Regulation of autophagy pathway phosphorylation and uses thereof

ABSTRACT

The invention relates to polypeptides and proteins known to function in the autophagy pathway that have novel phosphorylation sites. The invention also relates to antibodies specific to these polypeptides and proteins that are phosphorylated or not phosphorylated at novel phosphorylated sites. The invention also relates to methods of producing these antibodies and use of these antibodies in the treatment of diseases related to autophagocytosis.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No. 12/505,281, now U.S. Pat. No. 8,148,088, which claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application Ser. No. 61/082,174 filed Jul. 18, 2008 and U.S. Provisional Application Ser. No. 61/082,179 filed Jul. 18, 2008, the disclosures of which are herein incorporated by reference in their entirety.

REFERENCE TO SEQUENCE LISTING SUBMITTED VIA EFS-WEB

The entire content of the following electronic submission of the sequence listing via the USPTO EFS-WEB server, as authorized and set forth in MPEP §1730 II.B.2(a)(C), is incorporated herein by reference in its entirety for all purposes. The sequence listing is identified on the electronically filed text file as follows:

File Name Date of Creation Size (bytes) 549132000401Seqlist.txt May 30, 2012 1,032,007 bytes

TECHNICAL FIELD

The claimed compositions, methods, and kits are directed to antibodies to detect autophagy proteins in either the phosphorylated or nonphosphorylated forms.

BACKGROUND ART

Autophagy is a process whereby cells convert proteins and organelles into amino acids as a source of food. Many cells in the human body rely on autophagy to maintain homeostasis, especially when insulin levels are low. Autophagocytosis may play a role in human disease and aging. In eukayrotic cells autophagy occur constitutively at low levels in all cells to perform housekeeping functions such as destruction of dysfunctional organelles. Dramatic upregulation occurs (e.g., cytoplasmic and organelle turnover) in the presence of external stressors (starvation, hormonal imbalance, oxidation, extreme temperature, and infection), and internal needs (generation of source materials for architectural remodeling, removal of protein aggregates). Autophagy is highly regulated through the coordinated action of various kinases, phosphatases, and guanosine triphosphatases (GTPases).

At least three different autophagy mechanisms are known, all of which result in targeting of cytosolic proteins and organelles to the lysosome in order to provide amino acids and energy in the form of catabolites. These types are macroautophagy, microautophagy, and chaperone-mediated autophagy.

Macroautophagy is a major inducible pathway for the general turnover of cytoplasmic constituents in eukaryotic cells and also plays a significant role in the degradation of active cytoplasmic enzymes and organelles during nutrient starvation. Macroautophagy involves the formation of double-membrane bound autophagosomes which enclose the cytoplasmic constituent targeted for degradation in a membrane bound structure, which then fuse with the lysosome (or vacuole) releasing a single-membrane bound autophagic bodies which are then degraded within the lysosome (or vacuole). MAP1A and MAP1B are microtubule-associated proteins which mediate the physical interactions between microtubules and components of the cytoskeleton. These proteins are involved in formation of autophagosomal vacuoles (autophagosomes). MAP1A and MAP1B each consist of a heavy chain subunit and multiple light chain subunits. Apg8a is one of the light chain subunits and can associate with either MAP1A or MAP1B. The precursor molecule is cleaved by APG4B/ATG4B to form the cytosolic form, Apg8a-I. This is activated by APG7L/ATG7, transferred to ATG3 and conjugated to phospholipid to form the membrane-bound form, Apg8a-II.

Microautophagy circumvents the autophagosomic step of macrophagy, and begins with the direct uptake of cytosolic material via invaginations and pinching off of the lysosomal membrane. The internalized cytosolic components are digested by lysosomal enzymes released when the vacuolar membrane disintegrates, as in macroautophagy.

In chaperone-mediated autophagy, specific chaperone proteins bind to target proteins containing a KFERQ (SEQ ID NO: 1) sequence and channel these proteins to the surface of the lysosome. These proteins bind to Lamp2a and are then transported across the lysosomal membrane with the assistance of lysosomal chaperones, after which they are degraded by vacuolar proteases.

Mizushima, et al., describes autophagy as promoting both cell survival and cell death. By maintaining homeostasis during times of cellular stress, autophagy generally promotes survival when it is controlled. See Mizushima, N., et al., “Autophagy fights disease through cellular self-digestion” Nature (2008) 451:1069-1075.

However, dramatic upregulation of autophagy via Beclin 1 overexpression brings about cell death. Mizushima, et al., describe how the autophagy and apoptosis pathways share many common regulatory factors, with the likelihood of significant cross-talk between these pathways in the cell. Since apoptosis is known to be implicated in human disease, autophagy also is likely an important phenomenon to target in order to treat disease.

Proteins that regulate autophagy in cancer cells make attractive therapeutic and diagnostic targets. Cancer cells rely on autophagy in order to evade anti-cancer treatments designed to reduce nutrient supply and enhance the stress on rapidly dividing cells. A compound that downregulates autophagy may be a useful additional drug in cancer treatment. Mizushima, et al., state that since autophagy may help prevent cancer, there is a potential need to target autophagy in a context-specific manner. The targeting of specific autophagy regulatory proteins rather than a targeting of autophagy in general may be critical in developing a treatment of cancer as well as new modes of diagnosing cancer.

Alterations in the autophagy degradation pathway have been described in normal brain aging and in age-related neurodegenerative diseases including Alzheimer's and Parkinson's diseases. See Nixon, R., “Autophagy in neurodegenerative disease: friend, foe, or turncoat?” Trends in Neurosciences (2006) 29(9):528-535. An improper clearance of proteins in these diseases may result either from a compromise in the autophagy degradation pathway or induced alterations in this pathway, and may result in neuron dysfunction and neuron loss. The targeting of specific autophagy regulatory proteins, rather than a targeting of autophagy in general, may be critical in developing a treatment of neurodegenerative diseases as well as new modes of diagnosing neurodegenerative diseases. Therefore, there exists a need to develop an assay to monitor the activity of autophagy proteins that does not rely exclusively on protein localization.

DISCLOSURE OF THE INVENTION

Several of the following aspects provide peptides comprising amino acids that are novel phosphorylation sites on various autophagy proteins. Several of the following aspects also provide antibodies that react specifically to the phosphorylated forms of these proteins, and antibodies that react specifically to the non-phosphorylated forms of these proteins.

In one aspect, the present disclosure provides an isolated autophagy peptide that comprises an amino acid sequence selected from the group consisting of the sequences set forth in Table 1, wherein the x residue is nonphosphorylated or phosphorylated serine, threonine, or tyrosine, and with the proviso that the peptide is not a full-length autophagy protein comprising an amino acid sequence set forth in Table 2. The peptides of this embodiment are referred to as “autophagy peptides”.

In some embodiments, an isolated peptide of the present disclosure comprises an amino sequence found in Table 3. The peptides of this embodiment are a subset of possible autophagy peptides.

In another embodiment, isolated peptides of the present disclosure comprise an amino acid sequence found in Table 4. In some embodiments, the x residue may be phosphorylated. In some embodiments, the x residue may be nonphosphorylated.

In another aspect, the disclosure provides for an immunogen, which comprises an autophagy peptide and immune response potentiator.

In another aspect, the disclosure provides for a multiple antigenic peptide (MAP), which comprises a branched oligolysine core conjugated with a plurality of isolated autophagy peptides.

In another aspect, the disclosure provides for a method for producing an antibody to an autophagy polypeptide. The method comprises introducing an isolated autophagy peptide comprising a sequence set forth in Table 1 to a mammal in an amount sufficient to produce an antibody to the autophagy peptide; and recovering the antibody from the mammal.

In another aspect, the disclosure provides for a kit for producing an antibody to an autophagy polypeptide. The kit comprises an isolated autophagy peptide comprising a sequence set forth in Table 1, a means for introducing the isolated autophagy peptide to a mammal in an amount sufficient to produce an antibody to the autophagy peptide, and a means for recovering the antibody from the mammal.

In another aspect, the disclosure provides for a method for producing an antibody to an autophagy polypeptide. The method comprises introducing an autophagy protein to a mammal in an amount sufficient to produce an antibody to the autophagy protein, recovering the antibody from the mammal, and affinity purifying an autophagy antibody that specifically binds to an epitope of the sequence in Table 3. This method is referred to below as the “method for producing an affinity-purified autophagy antibody” In one embodiment, the disclosure provides for an antibody to an autophagy polypeptide produced by this method.

In another aspect, the disclosure provides for a kit for producing an antibody to an autophagy polypeptide. The kit comprises an autophagy protein, a means for introducing the autophagy protein to a mammal in an amount sufficient to produce an antibody to the autophagy polypeptide, a means for recovering the antibody from the mammal, and an isolated autophagy peptide comprising a sequence from Table 1.

In another aspect, the disclosure provides for an isolated antibody that specifically binds to an epitope that comprises the amino acid residue x (also referred to herein as the “X residue”) in an amino acid sequence set forth in Table 3, wherein the x residue is either phosphorylated or nonphosphorylated serine, threonine, or tyrosine. In one embodiment, the epitope comprises the amino acid residue x in one amino acid sequence set forth in Table 3 and an amino acid residue of autophagy protein that is outside the same amino acid sequence set forth in Table 3. In another embodiment, the epitope comprises the amino acid residue x in one amino acid sequence set forth in Table 3 and amino acid residues of an autophagy protein that are outside the same amino acid sequence set forth in Table 3.

In another aspect, the disclosure provides for a method for detecting an autophagy protein or fragment comprising an amino acid sequence set forth in Table 4, wherein the x residue is either phosphorylated or nonphosphorylated serine, threonine, or tyrosine, in a sample. The method comprises the following steps. First, a sample containing or suspected of containing an autophagy protein or fragment comprising the amino acid sequence set forth in Table 4, wherein the x residue is either phosphorylated or nonphosphorylated, is contacted with an isolated antibody that specifically binds to an epitope that comprises the amino acid residue x in the amino acid sequence set forth in Table 4, wherein x is either phosphorylated or nonphosphorylated. The next step is assessing a complex formed between the autophagy protein or fragment, if present in the sample, and the antibody, to determine the presence, absence and/or amount of the autophagy protein or fragment in the sample.

In another aspect, the disclosure provides for a kit for detecting an autophagy protein or fragment comprising amino acid sequence set forth in Table 4 wherein x is serine or phosphoserine in a sample, which kit comprises, in a container, an isolated antibody that specifically binds to an epitope that comprises the amino acid residue x in the amino acid sequence set forth in Table 4, wherein x is serine or phosphoserine.

In another aspect, the disclosure provides for a method for treating a disease or disorder associated with abnormal phosphorylation status of an autophagy protein or fragment comprising amino acid sequence set forth in Table 4 wherein the x residue is either phosphorylated or nonphosphorylated, which method comprises administering, to a subject when such a treatment is needed or desired, a sufficient amount of an isolated antibody that specifically binds to an epitope that comprises the x residue in the amino acid sequence set forth in Table 4, wherein x is either phosphorylated or nonphosphorylated.

Another aspect is a method for identifying a kinase that phosphorylates an autophagy protein on the x residue. The method comprises the steps of: (1) providing autophagy polypeptide comprising an amino acid sequence listed in Table 1, wherein x is nonphosphorylated serine, threonine, or tyrosine; (2) contacting the autophagy polypeptide with a test protein and ATP under conditions suitable for the phosphorylation of the x residue of the autophagy polypeptide; and (3) assessing the phosphorylation status of the autophagy polypeptide to determine whether the test protein is a kinase for the autophagy protein on the x residue.

Another aspect is a method for identifying a modulator of a kinase that phosphorylates an autophagy protein on the x residue. The method comprises the steps of: (1) providing an autophagy polypeptide comprising an amino acid sequence selected from a sequence listed in Table 1, wherein the x residue is not phosphorylated; (2) contacting the autophagy polypeptide with a kinase that phosphorylates the protein on the residue indicated by x and ATP under conditions suitable for the phosphorylation of the x residue of the autophagy polypeptide in the presence or absence of a test substance; and assessing and comparing phosphorylation status of the autophagy polypeptide by the kinase to determine whether the test substance modulates the kinase.

Another aspect is a method for identifying a phosphatase that dephosphorylates an autophagy protein on a phosphorylated x residue. The method comprises the steps of: (1) providing an autophagy polypeptide comprising an amino acid sequence selected from the group consisting of a sequence listed in Table 1, wherein x is phosphorylated; (2) contacting the autophagy polypeptide with a test protein and H₂O under conditions suitable for the dephosphorylation of the phosphoserine residue of the autophagy polypeptide; and (3) assessing phosphorylation status of the autophagy polypeptide to determine whether the test protein is a phosphatase for the autophagy polypeptide on the x residue.

Another aspect is a method for identifying a modulator of a kinase that phosphorylates an autophagy protein on the x residue. The method comprises the steps of: (1) providing an autophagy polypeptide comprising an amino acid sequence listed in Table 1, wherein x is nonphosphorylated serine, threonine, or tyrosine; (2) contacting the autophagy polypeptide with a kinase that phosphorylates an autophagy polypeptide on the x residue and ATP under conditions suitable for the phosphorylation of the x residue of the autophagy polypeptide in the presence or absence of a test substance; and (3) assessing and comparing the phosphorylation status of the autophagy polypeptide by the kinase to determine whether the test substance modulates the kinase.

Another aspect is an isolated nucleic acid fragment which is comprised of a sequence of nucleotides encoding an autophagy peptide comprising an amino acid sequence selected from the group consisting of sequences set forth in Table 1, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine. The autophagy peptide is not a full-length autophagy protein comprising an amino acid sequence set forth in Table 2. The nucleic acid may be DNA. The nucleic acid may also be RNA.

Other objects, features, and technical advantages of the present invention will become more apparent from a consideration of the detailed description herein and from the accompanying drawings.

All publications, patents, patent applications, GenBank sequences and ATCC deposits, cited herein are hereby expressly incorporated by reference for all purposes.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a dot blot of an antibody that specifically binds to APG3L that is phosphorylated at tyrosine-18.

FIG. 2 shows a dot blot of an antibody that specifically binds to APG4A that is phosphorylated at serine-100.

FIG. 3 shows a dot blot of an antibody that specifically binds to APG4C that is phosphorylated at serine-166.

FIG. 4 shows a dot blot of an antibody that specifically binds to APG4C that is phosphorylated at serine-177.

FIG. 5 shows a dot blot of an antibody that specifically binds to APG4C that is phosphorylated at serine-398.

FIG. 6 shows a dot blot of an antibody that specifically binds to APG4C that is phosphorylated at serine-451.

FIG. 7 shows a dot blot of an antibody that specifically binds to APG4D that is phosphorylated at serine-15.

FIG. 8 shows a dot blot of an antibody that specifically binds to APG4D that is phosphorylated at serine-341.

FIG. 9 shows a dot blot of an antibody that specifically binds to APG4D that is phosphorylated at serine-467.

FIG. 10 shows a dot blot of an antibody that specifically binds to APG7L that is phosphorylated at serine-95.

FIG. 11 shows a dot blot of an antibody that specifically binds to APG9L1 that is phosphorylated at serine-735.

FIG. 12 shows a dot blot of an antibody that specifically binds to APG16L that is phosphorylated at serine-213.

FIG. 13 shows a dot blot of an antibody that specifically binds to APG16L that is phosphorylated at serine-287.

MODES OF CARRYING OUT THE INVENTION

For clarity of disclosure, and not by way of limitation, the detailed description of the invention is divided into the subsections that follow.

Definitions

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art to which this invention belongs. All patents, patent applications (published or unpublished), and other publications referred to herein are incorporated by reference in their entirety. If a definition set forth in this section is contrary to or otherwise inconsistent with a definition set forth in the patents, applications, published applications and other publications that are herein incorporated by reference, the definition set forth in this section prevails over the definition that is incorporated herein by reference.

As used herein, “a” or “an” means “at least one” or “one or more.”

As used herein, the term “autophagy protein” refers to one of the following proteins, as indicated by name and an exemplary NCBI accession number: APG-3L (NP_(—)071933), APG4A (NP_(—)443168), APG4B (NP_(—)037457), APG4C(NP_(—)835739), APG4D (NP_(—)116274), APG5L (NP_(—)004840), APG7L (NP_(—)006386), APG8b (NP_(—)073729), APG8c (NP_(—)073729), APG9L1 (NP_(—)076990), APG10L (NP_(—)113670), APG12L (NP_(—)004698), APG16L (NP_(—)110430), and BECN1 (NP_(—)003757).

As used herein, “antibody” is used in the broadest sense. Therefore, an “antibody” can be naturally occurring or man-made such as monoclonal antibodies produced by conventional hybridoma technology and/or a functional fragment thereof. Antibodies of the present invention comprise monoclonal and polyclonal antibodies as well as fragments containing the antigen-binding domain and/or one or more complementarity determining regions of these antibodies. Antibodies can be of any isotype including IgM, IgG, IgD, IgA and IgE, and any sub-Isotype, including IgG1, IgG2a, IgG2b, IgG3 and IgG4, IgE1, IgE2, etc. The light chains of the antibodies can either be kappa light chains or lambda light chains.

As used herein, “monoclonal antibody” refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the antibodies comprising the population are identical except for possible naturally occurring mutations that are present in minor amounts. As used herein, a “monoclonal antibody” further refers to functional fragments of monoclonal antibodies.

As used herein, the phrase “oligoclonal antibodies” refers to a predetermined mixture of distinct monoclonal antibodies. See, e.g., PCT publication WO 95/20401; U.S. Pat. Nos. 5,789,208 and 6,335,163.

As used herein, “peptide” includes all “mimetic” and “peptidomimetic” forms. The terms “mimetic” and “peptidomimetic” refer to a synthetic chemical compound which has substantially the same structural and/or functional characteristics of the polypeptides of the invention. The mimetic can be either entirely composed of synthetic, non-natural analogues of amino acids, or, is a chimeric molecule of partly natural peptide amino acids and partly non-natural analogs of amino acids. The mimetic can also incorporate any amount of natural amino acid conservative substitutions as long as such substitutions also do not substantially alter the mimetic's structure and/or activity. Routine experimentation will determine whether a mimetic is within the scope of the invention, i.e., that its structure and/or function is not substantially altered.

As used herein, “polypeptide” includes a molecular chain of amino acids linked through peptide bonds. “Polypeptide” does not refer to a specific length of the product. Thus, “peptides,” “oligopeptides,” and “proteins” are included within the definition of polypeptide.

As used herein, an “antigen”, includes any portion of a protein (peptide, protein fragment, full-length protein), wherein the protein is naturally occurring or synthetically derived, a cellular composition (whole cell, cell lysate or disrupted cells), an organism (whole organism, lysate or disrupted cells), a carbohydrate, a lipid, or other molecule, or a portion thereof, wherein the antigen elicits an antigen-specific immune response (humoral and/or cellular immune response).

As used herein, “mammal” refers to any of the mammalian class of species. Frequently, the term “mammal,” as used herein, refers to humans, human subjects or human patients.

As used herein, “treatment” means any manner in which the symptoms of a condition, disorder or disease are ameliorated or otherwise beneficially altered. Treatment also encompasses any pharmaceutical use of the compositions herein.

As used herein, “disease or disorder” refers to a pathological condition in an organism resulting from, e.g., infection or genetic defect, and characterized by identifiable symptoms.

As used herein, the term “subject” is not limited to a specific species or sample type. For example, the term “subject” may refer to a patient, and frequently a human patient. However, this term is not limited to humans and thus encompasses a variety of mammalian species.

As used herein, “afflicted” as it relates to a disease or disorder refers to a subject having or directly affected by the designated disease or disorder.

As used herein the term “sample” refers to anything which may contain an analyte for which an analyte assay is desired. The sample may be a biological sample, such as a biological fluid or a biological tissue. Examples of biological fluids include urine, blood, plasma, serum, saliva, semen, stool, sputum, cerebral spinal fluid, tears, mucus, amniotic fluid or the like. Biological tissues are aggregate of cells, usually of a particular kind together with their intercellular substance that form one of the structural materials of a human, animal, plant, bacterial, fungal or viral structure, including connective, epithelium, muscle and nerve tissues. Examples of biological tissues also include organs, tumors, lymph nodes, arteries and individual cell(s).

As used herein, the term “specifically binds” refers to the binding specificity of a specific binding pair. Recognition by an antibody of a particular target in the presence of other potential targets is one characteristic of such binding. “Binding component member” refers to a member of a specific binding pair, i.e., two different molecules wherein one of the molecules specifically binds with the second molecule through chemical or physical means. The two molecules are related in the sense that their binding with each other is such that they are capable of distinguishing their binding partner from other assay constituents having similar characteristics. The members of the binding component pair are referred to as ligand and receptor (antiligand), specific binding pair (sbp) member and sbp partner, and the like. A molecule may also be a sbp member for an aggregation of molecules; for example an antibody raised against an immune complex of a second antibody and its corresponding antigen may be considered to be an sbp member for the immune complex.

As used herein the term “does not specifically bind” refers to the specificity of particular antibodies or antibody fragments. Antibodies or antibody fragments that do not specifically bind a particular moiety generally contain a specificity such that a large percentage of the particular moiety would not be bound by such antibodies or antibody fragments. This percentage generally lies within the acceptable cross reactivity percentage with interfering moieties of assays utilizing antibodies directed to detecting a specific target. Frequently, antibodies or antibody fragments of the present disclosure do not specifically bind greater than about 90% of an interfering moiety, although higher percentages are clearly contemplated and preferred. For example, antibodies or antibody fragments of the present disclosure do not specifically bind about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, and about 99% or more of an interfering moiety. Less occasionally, antibodies or antibody fragments of the present disclosure do not specifically bind greater than about 70%, or greater than about 75%, or greater than about 80%, or greater than about 85% of an interfering moiety.

As used herein the term “isolated” refers to material removed from its original environment, and is altered from its natural state. For example, an isolated polypeptide could be coupled to a carrier, and still be “isolated” because that polypeptide is not in its original environment.

As used herein, the term “X residue” refers to residues of autophagy proteins that are phosphorylation sites, as depicted in Tables 4 and 5. Table 4 shows the site of the x residue, with a label “X”. Table 5 shows the x residue in underlined form, with the x residue as threonine, serine, or tyrosine. The phosphorylation state of the x residue is typically described as phosphorylated or nonphosphorylated.

As used herein, the term “autophagy polypeptide” refers to a polypeptide comprising an entire autophagy protein or a fragment of an entire autophagy protein.

As used herein, the term “autophagy peptide” refers to a peptide comprising at least four consecutive amino acid residues of a sequence from Table 4. The “X” residue may be phosphorylated or not phosphorylated.

As used herein, the term “phosphorylated autophagy peptide” refers to an autophagy peptide that is phosphorylated at the x residue.

As used herein, the term “nonphosphorylated” when modifying “autophagy peptide” refer to an autophagy peptide that is not phosphorylated at the x residue.

The titles of each section and the examples of the following specification are not intended to be limiting.

The disclosure is based on the discovery of novel phosphorylation sites in a variety of proteins that play a role in autophagy. Throughout the specification, these proteins are referred to as autophagy proteins, whose names and an exemplary full-length sequence from a species are found in Table 2. The phosphorylation sites are on threonine, serine, and tyrosine residues in the autophagy proteins. Subsequences of these autophagy proteins are listed in Table 5, which further indicates the residue that is phosphorylated as underlined. The phosphorylated residue is represented by the letter x in the peptides shown in Tables 1, 3, and 4.

As a result of the identification of the novel sites of phosphorylation, peptide antigens may now be designed to raise phospho-specific antibodies that bind autophagy proteins when phosphorylated at the residue indicated by the letter x in the peptide (“X residue”). Furthermore, non-phosphospecfic antibodies may be designed that bind autophagy proteins when not phosphorylated at the x residue.

The epitopic site of the antibodies disclosed may be the sequences shown in Tables 1 and 3, with x represented the phosphorylation site as described in these tables. Epitopic sequences may be as short as four bases, with the possible epitopes shown in Table 1. Epitopic sequences may be longer than four bases, with possible epitopes having longer sequence shown in Table 3. Peptides having a sequence that includes the epitopic site are disclosed.

Autophagy Proteins

The following autophagy proteins may play a role in autophagy and are also phosphorylated. Autophagy peptides are comprised of a sequence within the autophagy proteins that encompass the phosphorylation site, which is indicated as an “X”. The autophagy peptide may have sequences that correspond to epitopes having sequence set forth in Table 1, wherein the x residue is either phosphorylated or nonphosphorylated serine, threonine, or tyrosine. The autophagy peptide may be comprised of a sequence having at least five residues that is found in Table 3. For any of the above autophagy peptides, the x residue is either phosphorylated or nonphosphorylated.

The autophagy peptide may be comprised of a sequence found in Table 4, in which the x residue is either phosphorylated or nonphosphorylated serine, threonine, or tyrosine. These sequences, as well as the above shorter sequences of this sequence, may be particularly strong antigens for the production of antibodies.

The autophagy peptide comprising the above sequences may not be the full length autophagy protein in any organism that is comprised of a sequence listed in Table 2.

In another embodiment, an isolated peptide of the present disclosure comprises an amino acid sequence set forth in Table 4. In some embodiments, the x residue of serine, threonine, or tyrosine may be nonphosphorylated. In some embodiments, the x residue of serine, threonine, or tyrosine may be phosphorylated.

Pharmaceutical Compositions

In some embodiments, the disclosure provides for a pharmaceutical composition comprising a pharmaceutically acceptable carrier, an excipient, and an isolated autophagy peptide. The pharmaceutical compositions can be used to promote or otherwise enhance the rate of autophagy in vertebrate animals including mammals. Alternatively, the pharmaceutical compositions can be used to inhibit or reduce the rate of autophagy in vertebrate animals, including mammals. Accordingly, the compositions are considered useful for treating or preventing a variety of conditions including ischemic brain injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, prion diseases and polyglutamine disorders including Huntington's disease and various spinocerebellar ataxias, transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease, breast cancer, ovarian cancer, brain cancer, pancreatic cancer, esophageal cancer, colorectal cancer, liver cancer, prostate cancer, renal cancer, lung cancer, Myocardial ischemia, cardiac remodeling, cardiomyopathy, hemodynamic stress, myocardial hypertrophy, Neuronal ceroid-lipofuscinosis (adult and juvenile), Multiple Sulfatase Deficiency (MSD) and Mucopolysaccharidosis type IIIA, Batten disease, Niemann-Pick C, Danon disease, Pompe disease, and dysfunction of innate and adaptive immunity against intracellular pathogens.

The peptide compounds may be formulated into the compositions as neutral or salt forms. Pharmaceutically acceptable non-toxic salts include the acid addition salts (formed with the free amino groups) and which are formed by reaction with inorganic acids such as, for example, hydrochloric, sulfuric or phosphoric acids, or organic acids such as, for example, acetic, oxalic, tartaric, mandelic, citric, malic, and the like. Salts formed with the free carboxyl groups may be derived from inorganic bases such as, for example, sodium, potassium, ammonium, calcium, or ferric hydroxides, and such organic bases such as amines, i.e., isopropylamine, trimethylamine, 2-ethylamino ethanol, histidine, procaine, and the like.

An autophagy peptide is suitably administered to a subject, e.g., a human or a non-human mammal, such as a domestic animal. The amount administered may vary depending on various factors including, but not limited to, the agent chosen, the disease, and whether prevention or treatment is to be achieved. The peptides may be administered locally or systemically. Administration of the therapeutic agents may be continuous or intermittent, depending, for example, upon the recipient's physiological condition, whether the purpose of the administration is therapeutic or prophylactic, and other factors known to skilled practitioners. The administration of the agents of the invention may be essentially continuous over a preselected period of time or may be in a series of spaced doses.

One or more suitable unit dosage forms comprising an autophagy peptide can be administered by a variety of routes including oral, or parenteral, including by rectal, buccal, vaginal and sublingual, transdermal, subcutaneous, intravenous, intramuscular, intraperitoneal, intrathoracic, intracoronary, intrapulmonary and intranasal routes. The dosage form may optionally be formulated for sustained release. The formulations may, where appropriate, be conveniently presented in discrete unit dosage forms and may be prepared by any of the methods well known to pharmacy. Such methods may include the step of bringing into association the therapeutic agent with liquid carriers, solid matrices, semi-solid carriers, finely divided solid carriers or combinations thereof, and then, if necessary, introducing or shaping the product into the desired delivery system.

When the autophagy peptide is prepared for oral administration, it is preferably combined with a pharmaceutically acceptable carrier, diluent or excipient to form a pharmaceutical formulation, or unit dosage form. The total active ingredients in such formulations comprise from 0.1 to 99.9% by weight of the formulation. By “pharmaceutically acceptable” it is meant the carrier, diluent, excipient, and/or salt must be compatible with the other ingredients of the formulation, and not deleterious to the recipient thereof. The active ingredient for oral administration may be present as a powder or as granules; as a solution, a suspension or an emulsion; or in achievable base such as a synthetic resin for ingestion of the active ingredients from a chewing gum. The active ingredient may also be presented as a bolus, electuary or paste. A useful reference describing pharmaceutically acceptable carriers, diluents and excipients is Remington's Pharmaceutical Sciences (Mack Publishing Co. N.J. USA, 1991) which is incorporated herein by reference. Supplementary active compounds can also be incorporated into the compositions.

Pharmaceutical formulations containing an autophagy protein can be prepared by procedures known in the art using well known and readily available ingredients. For example, the natriuretic peptide can be formulated with common excipients, diluents, or carriers, and formed into tablets, capsules, suspensions, powders, and the like. Examples of excipients, diluents, and carriers that are suitable for such formulations include the following fillers and extenders such as starch, sugars, mannitol, and silicic derivatives; binding agents such as carboxymethyl cellulose, HPMC and other cellulose derivatives, alginates, gelatin, and polyvinyl-pyrrolidone; moisturizing agents such as glycerol; disintegrating agents such as calcium carbonate and sodium bicarbonate; agents for retarding dissolution such as paraffin; resorption accelerators such as quaternary ammonium compounds; surface active agents such as cetyl alcohol, glycerol monostearate; adsorptive carriers such as kaolin and bentonite; and lubricants such as talc, calcium and magnesium stearate, and solid polyethyl glycols.

For example, tablets or caplets containing the nucleic acid molecule or peptide of the invention can include buffering agents such as calcium carbonate, magnesium oxide and magnesium carbonate. Caplets and tablets can also include inactive ingredients such as cellulose, pregelatinized starch, silicon dioxide, hydroxy propyl methyl cellulose, magnesium stearate, microcrystalline cellulose, starch, talc, titanium dioxide, benzoic acid, citric acid, corn starch, mineral oil, polypropylene glycol, sodium phosphate, and zinc stearate, and the like. Hard or soft gelatin capsules containing the nucleic acid molecule or peptide of the invention can contain inactive ingredients such as gelatin, microcrystalline cellulose, sodium lauryl sulfate, starch, talc, and titanium dioxide, and the like, as well as liquid vehicles such as polyethylene glycols (PEGs) and vegetable oil. Moreover, enteric coated caplets or tablets of the nucleic acid molecule or peptide of the invention are designed to resist disintegration in the stomach and dissolve in the more neutral to alkaline environment of the duodenum.

The autophagy peptide may be prepared in an injectable formulation. Injectable preparations, for example sterile injectable aqueous or oleaginous suspensions, are formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation can also be a sterile injectable solution or suspension in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or di-glycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables.

Autophagy Polypeptide Immunogens

The autophagy peptide may be used as an immunogen, with an exemplary use being to generate antibodies. The autophagy peptide may be phosphorylated or not at the residue indicated by x in the sequences of Table 5. In some embodiments, the isolated autophagy peptide of the above embodiments may be conjugated to a carrier to enhance the peptide's immunogenicity. Use of carriers while immunizing the animal is preferred when producing antibodies against an autophagy peptide. It is generally appreciated in the art that antigens must be at least 10 kDa in order to elicit a satisfactory immune response. The size of an antigen can be effectively increased by association of the antigen with a carrier.

The carrier may be a carrier protein. Alternatively, the autophagy peptide and the carrier protein may be part of a fusion protein. Exemplary carriers include, but are not limited to, Keyhole limpet cyanin, BSA, cationized BSA, ovalbumin, blue carrier immunogenic protein, avidin, BTG, bovine G globulin, bovine Immunoglobulin G (BlgG), bovine thyroglobulin, conalbumin, colloidal gold, edestin, exoprotein A (recombinant) from P. aeruginosa, hemocyanin from crab P. camtschatica, Helix promatia Hemocyanin (HPH), HSA, KTI (Kunitz trypsin inhibitor from soybeans), LPH (Heamocyanin from Limulus polyphemus), Pam3Cys-Th, polylysine, porcine thyroglobulin (PTG), purified protein derivative (PPD), rabbit serum albumin (RSA), soybean trypsin inhibitor (STI), sunflower globulin (SFG), and Tetanus toxoid. The carrier protein may be coupled to the peptide as described in Lateef, S., et al., J. Biomol. Tech. (2007) 8:173-176.

In another aspect, the immunogen may comprise an autophagy polypeptide and an immune response potentiator. In some embodiments, the immune response potentiator may be Bacille Calmette-Guerin (BCG), Corynebacterium Parvum, Brucella abortus extract, glucan, levamisole, tilorone, an enzyme or a non-virulent virus.

Multiple Antigenic Peptide

In another aspect, a multiple antigenic peptide (MAP) is provided, which MAP comprises a branched oligolysine core conjugated with a plurality of autophagy polypeptides as described herein. On occasion, the branched oligolysine core comprises 3, 7 or 15 lysine residues, also on occasion, the MAP comprises 4, 8 or 16 copies of the autophagy peptide. The plurality of the autophagy peptide comprises the same or different autophagy peptides. In some embodiments, the plurality of the autophagy peptide is conjugated to the branched oligolysine core via a spacer. Frequently, the spacer may be one or more amino acid residues. Multiple antigenic peptides comprise generally known technology. See, e.g., Adermann, K., et al., Innovations and Perspectives in Solid Phase Synthesis 429-432 (R. Epton, ed., Mayflower Worldwide 1994). Furthermore, in some embodiments, the plurality of autophagy peptides is comprised of the same peptide or different peptides.

Method of Producing an Antibody Against an Autophagy Protein

In another aspect is a method for producing an antibody to an autophagy polypeptide. The method comprises introducing an isolated an autophagy peptide into a mammal in an amount sufficient to produce an antibody to the autophagy peptide and recovering the antibody from the mammal. This method and variations thereof in order to enhance antibody specificity can be appreciated by one of skill in the art.

In one embodiment of this aspect, the x residue in the isolated autophagy peptide is not phosphorylated and the method is used to produce an antibody to an autophagy polypeptide that is not phosphorylated at the corresponding serine. In practicing this and subsequent embodiments of this aspect, one of skill in the art may test the specificity of the produced antibody against an autophagy polypeptide phosphorylated or not phosphorylated at the x residue in order to determine specificity.

In another embodiment of this aspect, the x residue in the isolated autophagy peptide is phosphorylated and the method is used to produce an antibody to a phosphorylated autophagy polypeptide. This embodiment may further comprise a step of removing an antibody that binds to an isolated autophagy peptide having a sequence in which the x residue is not phosphorylated.

In some embodiments of the method for producing an autophagy antibody, the isolated autophagy peptide is conjugated to a carrier to enhance the peptide's immunogenicity. Alternatively, in some embodiments, the isolated autophagy peptide is comprised in an immunogen comprised of an isolated autophagy peptide and an immune response potentiator. The carrier, immunogen, and immune response potentiator may be in any of the forms described above.

In another embodiment of the method for producing an autophagy antibody, the isolated autophagy peptide is comprised in a multiple antigenic peptide (MAP), in which the MAP comprises a branched oligolysine core conjugated with a plurality of isolated autophagy peptides. The MAP may be in any of the forms as described above.

Method of Producing an Autophagy Polypeptide Antibody with Subsequent Affinity Purification

Another aspect is a method for producing an antibody to an autophagy polypeptide. The method comprises introducing an autophagy polypeptide to a mammal in an amount sufficient to produce an antibody to the autophagy polypeptide, recovering the antibody from the mammal, and affinity purifying an antibody that specifically binds to an epitope having a sequence listed in Table 1. The autophagy polypeptide may be a full-length sequence listed in Table 4. The autophagy polypeptide may be a truncated form of the full-length sequence listed in Table 4 that at least comprises the sequence of the autophagy peptide used in affinity purification. It will be appreciated by one of skill in the art that affinity purification of the antibody leads to an enrichment of antibodies that specifically bind to the autophagy peptide used in affinity purification, as well as a high possibility of enriching for antibodies that bind to epitopes containing phosphorylated “X residues”.

In some embodiments of this method, the autophagy polypeptide is nonphosphorylated and the method is used to produce an antibody that specifically binds to a nonphosphorylated autophagy polypeptide. As an example, the autophagy polypeptide used to immunize the animal is not phosphorylated at the x residue and affinity purification is performed using a nonphosphorylated autophagy peptide.

In some embodiments of this method, the x residue in the amino acid sequence set forth in Table 4 of is phosphorylated and the method is used to produce an antibody to a phosphorylated autophagy polypeptide. As an example, the autophagy polypeptide used to immunize the animal is phosphorylated at the x residue and affinity purification is performed using the autophagy polypeptide that is phosphorylated at the x residue. Optionally, this method further comprises a step of removing an antibody that binds to an isolated nonphosphorylated autophagy peptide, wherein x is serine, threonine, or tyrosine. As an example, the antibody sample can be passed through a column containing bound nonphosphorylated autophagy peptide such that antibodies specific to nonphosphorylated autophagy peptide are removed by remaining bound to the column.

Kit for Preparing Antibody to an Autophagy polypeptide

A kit may be used to prepare an antibody to an autophagy polypeptide. The kit comprises an autophagy protein and a means for introducing the autophagy protein to a mammal in an amount sufficient to produce an antibody to the autophagy polypeptide. The kit also comprises a means for recovering the antibody from the mammal and an isolated autophagy polypeptide comprised of one of the sequences from Table 1. Another embodiment of the kit comprises an autophagy protein and a means for introducing the autophagy protein to a mammal in an amount sufficient to produce an antibody to an autophagy polypeptide.

One exemplary kit contains a full length autophagy protein and reagents containing appropriate immunogens, adjuvants, and buffers such that the autophagy polypeptide can be prepared for introduction into a mammal. The exemplary kit further contains an autophagy polypeptide as well as affinity purification columns that can be used to enrich for antibodies that specifically bind to the autophagy peptide.

Isolated Antibodies

Another aspect is an isolated antibody that specifically binds to an epitope that comprises the x residue in an amino acid sequence set forth in Table 4, wherein x residue is phosphorylated or nonphosphorylated. Multiple embodiments of this aspect are discussed as follows.

In one further embodiment of this aspect, the antibody is a monoclonal or polyclonal antibody or an antibody fragment.

In a further embodiment of this antibody, the epitope of the above antibody comprises both the amino acid residue x in the amino acid sequence set forth in Table 4 and an amino acid residue of the autophagy protein that is outside of the amino acid sequence set forth in Table 4. An exemplary epitope may arise from protein folding in which a residue outside set forth in Table 4 is brought into close proximity with the first epitope. Optionally, a kit may be prepared that is comprised of an antibody of this embodiment, a pharmaceutically acceptable carrier and an excipient.

In a third further embodiment of this antibody, the epitope comprises the amino acid x in the amino acid sequence set forth in Table 4 and amino acid residues of the autophagy protein that are outside of the amino acid sequence set forth in Table 4.

In a fourth further embodiment, the epitope is comprised in the amino acid sequence set forth in Table 4.

In another further embodiment, the epitope is comprised of a sequence set forth in Table 3.

In another further embodiment, the epitope is comprised of a sequence set forth in Table 1.

In another further embodiment, the antibody specifically binds to the epitope that comprises the amino acid residue x in the amino acid sequence set forth in Table 4, wherein the x residue is nonphosphorylated.

In another further embodiment, the antibody specifically binds to the epitope that comprises the amino acid residue x in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated.

In another further embodiment, the antibody specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is nonphosphorylated, but does not specifically bind to an epitope comprised in the amino acid sequence of Table 4, wherein the x residue is phosphorylated.

In another further embodiment, the antibody specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue of serine, threonine, or tyrosine is phosphorylated, but does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue of serine, threonine, or tyrosine is nonphosphorylated.

In another further embodiment of this antibody, the amino acid sequence set forth in Table 4 is comprised in an autophagy protein or fragment. In one variation of this embodiment, the antibody specifically binds to the full length autophagy protein when the x residue in a sequence set forth in Table 4 is nonphosphorylated, but does not specifically bind to the full length autophagy protein when the x residue is phosphorylated in the amino acid sequence set forth in Table 4. In another variation of this embodiment, the antibody specifically binds to the full length autophagy protein when the x residue is phosphorylated in the amino acid sequence set forth in Table 4, but does not specifically bind to the full length autophagy protein when the x residue is nonphosphorylated in the amino acid sequence set forth in Table 4. In a third variation of this embodiment, the antibody specifically binds to the full length autophagy protein at its natural conformation.

It will be appreciated by one of skill in the art, that there are many approaches to produce antibodies of this aspect. The following are some exemplary techniques of preparing antibodies.

Antibodies may be prepared using recombinant techniques to generate a Fab fragment that binds to an antigen. The Fab fragment may be generated by sequencing the amino acid residues of a desired monoclonal antibody and determining the sequence of the light chain and the variable and constant regions of the heavy chain that are associated with that particular light chain. Then, two peptides may be designed with these sequences. The peptides may be produced recombinantly in any system, preferably E. coli and B. subtilis, by designing a vector that contains sequence encoding these two peptides.

Animals are generally required for at least one stage of antibody production. The following exemplary animals may be used: rabbits, chickens, goats, guinea pigs, hamsters, horses, mice, rats, and sheep. Factors governing which animal to choose include: 1) the amount of antibody needed, 2) phylogenetic relationship between the donor of the antigen and the antibody producing animal and 3) the specific desired characteristics of the antibodies. If large amounts of antibody is the overriding concern, then horses, goats, and sheep may be preferred. If a distant phylogenetic relationship is important, then chickens are preferred. Mice and rats are preferred for monoclonal antibody production since only small amounts of antigen are needed to generate antibody producing cells needed for subsequent cloning. Rabbits are a preferred choice for laboratory scale polyclonal antibody production.

Various embodiments of this and other aspects use the following methods to enhance antibody production in an animal: use of carriers (i.e., keyhole limpet cyanin) and immune response potentiators (i.e., multiple antigen peptide such as branched oligolysine).

The amount of antigen used to immunize the animal may vary. Larger amounts of antigen are correlated with higher titer antibody production. For high titer antibody production, the following exemplary amounts of antigen may be used: 250-1,000 micrograms for a rabbit, 50-200 micrograms for a mouse, 150 to 500 micrograms for a guinea pig, 750 to 5,000 micrograms for a goat. Additionally, antibody production may be enhanced by administering small priming doses to an animal before a larger dose as above. The following exemplary amounts of antigen may be used for priming: 50-200 micrograms for a rabbit, 10-50 micrograms for a mouse, 50-500 micrograms for a guinea pig, 250 to 750 micrograms for a goat. Additional amounts of antigen may be administered in the form of a booster, which may be in an amount roughly equal to the priming doses.

Adjuvants may be combined with the antigen in order to stimulate the immune response. Exemplary adjuvants include Freund's complete, Freund's incomplete, Titermax, and Ribi.

Monoclonal antibodies may be produced using phage display techniques. An autophagy polypeptide may be attached to a support medium, such as a column. Phage that express a plurality of antibodies or fragments of antibodies, such as a phage display library, may be exposed to the autophagy polypeptide-bound support medium. An exemplary phage display library used for this purpose is described in Schofield, D., et al., Genome Biology (2007) 8(11):R254. Phage that bind to the support may then be further analyzed to determine if they express a molecule that may be an antibody to an autophagy polypeptide. Optionally, a phage display library may be used to isolate an antibody fragment that binds to an autophagy polypeptide. See Teunissen, S., et al., RNA (1998) 4:1124-1133, for an example of using phage display to isolate an antibody fragment.

An antibody may also be produced by using a clonal expansion of B cells to isolate an original light chain-heavy chain pairing. An example of this method is described in de Wildt, R., et al., J. Immunol. Methods (1997) 207:61-67.

Variant Antibodies

In some embodiments, the antibody can be an intact, four immunoglobulin chain antibody comprising two heavy chains and two light chains. The heavy chain of the antibody can be of any isotype including IgM, IgG, IgE, IgG, IgA or IgD or sub-Isotype including IgG1, IgG2, IgG3, IgG4, IgE1, IgE2, etc. The light chain can be a kappa light chain or a lambda light chain.

In some embodiments, an antibody may have fewer than 4 chains. Such exemplary antibodies include, but are not limited to, single chain antibodies, Camelid antibodies and the like and components of the antibody, including a heavy chain or a light chain. Such exemplary antibodies include small modular immunopharmaceuticals or SMIPs™, Fab and F(ab′)₂ fragments, etc. These antibodies may be produced by papain or pepsin digestion of antibodies. Papain digestion of antibodies produces two identical antigen-binding fragments, called “Fab” fragments, each with a single antigen-binding site, and a residual “Fc” fragment, whose name reflects its ability to crystallize readily. Pepsin treatment of an antibody yields an F(ab′)2 fragment that has two antigen-combining sites and is still capable of cross-linking antigen. The Fab fragment also contains the constant domain of the light chain and the first constant domain (CH1) of the heavy chain. Fab′ fragments differ from Fab fragments by the addition of a few residues at the carboxy terminus of the heavy chain CH1 domain including one or more cysteines from the antibody hinge region. Fab′-SH is the designation herein for Fab′ in which the cysteine residue(s) of the constant domains bear a free thiol group. F(ab′)₂ antibody fragments originally were produced as pairs of Fab′ fragments that have hinge cysteines between them. Other chemical couplings of antibody fragments are also known.

In some embodiments, the antibody may comprise an “Fv” domain. “Fv” usually refers to the minimum antibody fragment that contains a complete antigen-recognition and -binding site. This region consists of a dimer of one heavy- and one light-chain variable domain in tight, non-covalent association. It is in this configuration that the three CDRs of each variable domain interact to define an antigen-binding site on the surface of the V_(H)-V_(L) dimer. Collectively, the CDRs confer antigen-binding specificity to the antibody.

In some embodiments, the antibody may have a single variable domain (or half of an Fv comprising three CDRs specific for an antigen), since the single variable domain may have the ability to recognize and bind antigen, although likely at a lower affinity than the entire binding site.

In some embodiments, the antibody comprises a single-chain Fv antibody fragment. “Single-chain Fv” or “scFv” antibody fragments comprise the V_(H) and V_(L) domains of an antibody, wherein these domains are present in a single polypeptide chain. In certain embodiments, the Fv polypeptide further comprises a polypeptide linker between the VH and V_(L) domains that enables the scFv to form the desired structure for antigen binding. For a review of scFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore, eds. (Springer-Verlag: New York, 1994), pp. 269-315.

In some embodiments, the antibody may comprise a SMIP. SMIPs are a class of single-chain peptides engineered to include a target binding region and effector domain (CH2 and CH3 domains). See, e.g., U.S. Patent Application Publication No. 20050238646. The target binding region may be derived from the variable region or CDRs of an antibody, e.g., a phosphorylation site-specific antibody of the application. Alternatively, the target binding region is derived from a protein that binds a phosphorylation site.

In some embodiments, a therapeutic agent may be placed on one arm of the antibody. The therapeutic agent can be a drug, toxin, enzyme, DNA, radionuclide, etc.

In some embodiments, the antigen-binding fragment can be a diabody. The term “diabody” refers to small antibody fragments with two antigen-binding sites, which fragments comprise a heavy-chain variable domain (V_(H)) connected to a light-chain variable domain (V_(L)) in the same polypeptide chain (V_(H)-V_(L)). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites. Diabodies are described more fully in, for example, EP 404097; WO 93/11161; and Hollinger, et al., Proc. Natl. Acad. Sci. USA (1993) 90:6444-6448.

In some embodiments, antibodies may comprise camelid antibodies. Camelid antibodies refer to a unique type of antibodies that are devoid of light chain, initially discovered from animals of the camelid family. The heavy chains of camelid antibodies bind their antigen by one single domain, the variable domain of the heavy immunoglobulin chain, referred to as VHH. VHHs show homology with the variable domain of heavy chains of the human VHIII family. The VHHs obtained from an immunized camel, dromedary, or llama have a number of advantages, such as effective production in microorganisms such as Saccharomyces cerevisiae.

In some embodiments, the antibodies can be humanized, chimerized, deimmunized, or fully human. Numerous publications set forth the many types of antibodies and the methods of engineering such antibodies. For example, see U.S. Pat. Nos. 6,355,245; 6,180,370; 5,693,762; 6,407,213; 6,548,640; 5,565,332; 5,225,539; 6,103,889; and 5,260,203. The chimeric antibody is an antibody having portions derived from different antibodies. For example, a chimeric antibody may have a variable region and a constant region derived from two different antibodies. The donor antibodies may be from different species. In certain embodiments, the variable region of a chimeric antibody is non-human, e.g., murine, and the constant region is human.

The genetically altered antibodies used in the invention include CDR grafted humanized antibodies. In one embodiment, the humanized antibody comprises heavy and/or light chain CDRs of a non-human donor immunoglobulin and heavy chain and light chain frameworks and constant regions of a human acceptor immunoglobulin. The method of making humanized antibody is disclosed in U.S. Pat. Nos. 5,530,101 ; 5,585,089; 5,693,761 ; 5,693,762; and 6,180,370 each of which is incorporated herein by reference in its entirety.

In some embodiments, the antibody may be an “antigen-binding fragment of an antibody”, which is any portion of an antibody that retains specific binding of the intact antibody. An exemplary antigen-binding fragment of an antibody is the heavy chain and/or light chain CDR, or the heavy and/or light chain variable region. Antigen-binding fragments of the antibodies of the invention, which retain the binding specificity of the intact antibody, are also included in the invention. Examples of these antigen-binding fragments include, but are not limited to, partial or full heavy chains or light chains, variable regions, or CDR regions of any phosphorylation site-specific antibodies described herein.

In some embodiments, the antibody may be an immunoglobulin chain comprised in order from 5′ to 3′, of a variable region and a constant region. The variable region may comprise three complementarity determining regions (CDRs), with interspersed framework (FR) regions for a structure FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. In these embodiments, the antibody may further comprise heavy or light chain variable regions, framework regions and CDRs.

In some embodiments, the antibody may comprise a heavy chain constant region that comprises some or all of a CH1 region, hinge, CH2 and CH3 region.

In some embodiments, the antibody may have an binding affinity (K_(D)) of 1×10⁷ M or less. In other embodiments, the antibody binds with a K_(D) of 1×10⁸ M, 1×10⁹ M, 1×10¹⁰ M, 1×10¹¹ M, 1×10¹² M or less. In certain embodiments, the KD is 1 μM to 500 μM, between 500 μM to 1 μM, between 1 μM to 100 nM, or between 100 mM to 10 tiM.

In some embodiments, the antibodies may be genetically-altered, wherein the amino acid sequence of the native antibody has been varied. Because of the relevance of recombinant DNA techniques to this application, one need not be confined to the sequences of amino acids found in natural antibodies; antibodies can be redesigned to obtain desired characteristics. The possible variations are many and range from the changing of just one or a few amino acids to the complete redesign of, for example, the variable or constant region. Changes in the constant region may be made in order to improve or alter characteristics, such as complement fixation, interaction with membranes and other effector functions. Changes in the variable region may be made in order to improve the antigen binding characteristics. Modified antibodies may provide improved stability or/and therapeutic efficacy. Examples of modified antibodies include those with conservative substitutions of amino acid residues, and one or more deletions or additions of amino acids that do not significantly deleteriously alter the antigen binding utility. Substitutions can range from changing or modifying one or more amino acid residues to complete redesign of a region as long as the therapeutic utility is maintained. Antibodies can be modified post-translationally (e.g., acetylation, and/or phosphorylation) or can be modified synthetically (e.g., the attachment of a labeling group).

In preferred embodiments, genetically altered antibodies are functionally equivalent to the above-mentioned natural antibodies.

Oligoclonal antibodies may be used in various embodiments. In some embodiments, oligoclonal antibodies consisting of a predetermined mixture of antibodies against one or more epitopes are generated in a single cell. In other embodiments, oligoclonal antibodies comprise a plurality of heavy chains capable of pairing with a common light chain to generate antibodies with multiple specificities (e.g., PCT publication WO 04/009618). It is appreciated by one of skill in the art that oligoclonal antibodies are particularly useful when it is desired to target multiple epitopes on a single target molecule. In view of the assays and epitopes disclosed herein, those skilled in the art can generate or select antibodies or mixtures of antibodies that are applicable for an intended purpose and desired need.

Recombinant antibodies against the novel phosphorylation sites identified in the disclosure may be used in various embodiments. These recombinant antibodies have the same amino acid sequence as the natural antibodies or have altered amino acid sequences of the natural antibodies in the present application. They can be made in any expression systems including both prokaryotic and eukaryotic expression systems or using phage display methods (see, e.g., Dower, et al., WO91/17271 and McCafferty, et al., WO92/01047; U.S. Pat. No. 5,969,108, which are herein incorporated by reference in their entirety).

In some embodiments, antibodies have variant constant or Fc regions. Such antibodies can be useful in modulating effector functions, i.e., antigen-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Such antibodies may be useful in instances where a parent singling protein is expressed in normal tissue; variant antibodies without effector function in these instances may elicit the desired therapeutic response while not damaging normal tissue.

In some embodiments, the antibody fragments are truncated chains (truncated at the carboxyl end). These truncated chains may possess one or more immunoglobulin activities (e.g., complement fixation activity). Examples of truncated chains include, but are not limited to, Fab fragments (consisting of the VL, VH, CL and CH1 domains); Fd fragments (consisting of the VH and CH1 domains); Fv fragments (consisting of VL and VH domains of a single chain of an antibody); dAb fragments (consisting of a VH domain); isolated CDR regions; (FaW)₂ fragments, bivalent fragments (comprising two Fab fragments linked by a disulphide bridge at the hinge region). The truncated chains can be produced by conventional biochemical techniques, such as enzyme cleavage, or recombinant DNA techniques, each of which is known in the art. These polypeptide fragments may be produced by proteolytic cleavage of intact antibodies by methods well known in the art, or by inserting stop codons at the desired locations in the vectors using site-directed mutagenesis, such as after CH1 to produce Fab fragments or after the hinge region to produce (Fab′)₂ fragments. Single chain antibodies may be produced by joining VL- and VH-coding regions with a DNA that encodes a peptide linker connecting the VL and VH protein fragments.

In some embodiments, single chain antibodies, and chimeric, humanized or primatized (CDR-grafted) antibodies, as well as chimeric or CDR— grafted single chain antibodies, comprising portions derived from different species, are also encompassed by the present disclosure as antigen-binding fragments of an antibody. The various portions of these antibodies can be joined together chemically by conventional techniques, or can be prepared as a contiguous protein using genetic engineering techniques. For example, nucleic acids encoding a chimeric or humanized chain can be expressed to produce a contiguous protein. See, e.g., U.S. Pat. Nos. 4,816,567 and 6,331,415; U.S. Pat. No. 4,816,397; European Patent No. 0,120,694; WO86/01533; European Patent No. 0,194,276 B1; U.S. Pat. No. 5,225,539; and European Patent No. 0,239,400 B1. See also, Newman, et al., BioTechnology (1992) 10:1455-1460, regarding primatized antibody. See, e.g., Ladner, et al., U.S. Pat. No. 4,946,778; and Bird, et al., Science (1988) 242:423-426), regarding single chain antibodies.

In addition, functional fragments of antibodies, including fragments of chimeric, humanized, primatized or single chain antibodies, can also be produced. Functional fragments of the subject antibodies retain at least one binding function and/or modulation function of the full-length antibody from which they are derived.

Since the immunoglobulin-related genes contain separate functional regions, each having one or more distinct biological activities, the genes of the antibody fragments may be fused to functional regions from other genes (e.g., enzymes, U.S. Pat. No. 5,004,692, which is incorporated by reference in its entirety) to produce fusion proteins or conjugates having novel properties.

In some embodiments, non-Immunoglobulin binding polypeptides are also contemplated. For example, CDRs from an antibody disclosed herein may be inserted into a suitable non-Immunoglobulin scaffold to create a non-immunoglobulin binding polypeptide. Suitable candidate scaffold structures may be derived from, for example, members of fibronectin type III and cadherin superfamilies.

Some embodiments may comprise other equivalent non-antibody molecules, such as protein binding domains or aptamers, which bind, in a phospho-specific manner, to an amino acid sequence comprising a novel phosphorylation site of the invention. See, e.g., Neuberger, et al., Nature (1984) 312:604. Aptamers are oligonucleic acid or peptide molecules that bind a specific target molecule. DNA or RNA aptamers are typically short oligonucleotides, engineered through repeated rounds of selection to bind to a molecular target. Peptide aptamers typically consist of a variable peptide loop attached at both ends to a protein scaffold. This double structural constraint generally increases the binding affinity of the peptide aptamer to levels comparable to an antibody (nanomolar range).

In some embodiments, phosphorylation site-specific antibodies may be conjugated with immunotoxins. Conjugates that are immunotoxins including antibodies have been widely described in the art. The toxins may be coupled to the antibodies by conventional coupling techniques or immunotoxins containing protein toxin portions can be produced as fusion proteins. In certain embodiments, antibody conjugates may comprise stable linkers and may release cytotoxic agents inside cells (see U.S. Pat. Nos. 6,867,007 and 6,884,869). The conjugates of the present application can be used in a corresponding way to obtain such immunotoxins. Illustrative of such immunotoxins are those described by Byers, et al., Seminars Cell Biol (1991) 2:59-70 and by Fanger, et al., Immunol Today (1991) 12:51-54. Exemplary immunotoxins include radiotherapeutic agents, ribosome-Inactivating proteins (RIPs), chemotherapeutic agents, toxic peptides, or toxic proteins.

Antibody Pharmaceutical Compositions

Another aspect is a pharmaceutical composition that comprises an antibody of any other aspect disclosed. The pharmaceutical composition may further comprise a carrier. Suitable carriers include any material that when combined with the therapeutic composition retains the anti-tumor function of the therapeutic composition and is generally non-reactive with the patient's immune system. Examples include, but are not limited to, any of a number of standard pharmaceutical carriers such as sterile phosphate buffered saline solutions, bacteriostatic water, and the like (see, generally, Remington's Pharmaceutical Sciences, 16th Edition, A. Osal., Ed., 1980). PEG may be used as a pharmaceutical carrier. PEG may be covalently attached to the antibody in the pharmaceutical composition.

Method for Detecting an Autophagy Protein

Another aspect is a method for detecting an autophagy protein or fragment comprising an amino acid sequence set forth in Table 4, wherein the x residue is either phosphorylated or nonphosphorylated, in a sample. The method comprises contacting a sample containing or suspected of containing an autophagy protein or fragment comprising the amino acid sequence set forth in Table 4, wherein the x residue is either phosphorylated or nonphosphorylated serine, threonine, or tyrosine, with an isolated antibody that specifically binds to an epitope that comprises the x residue of the sequence set forth in Table 4, wherein x is either phosphorylated or nonphosphorylated; and assessing a complex formed between the autophagy protein or fragment, if present in the sample, and the antibody, to determine the presence, absence and/or amount of the autophagy protein or fragment in the sample.

In an embodiment of this method, the epitope comprises the amino acid residue x in the sequence set forth in Table 4 and an amino acid residue of the autophagy protein that is outside the amino acid sequence set forth in Table 4.

In another embodiment of this method, the epitope comprises the amino acid residue x in the amino acid sequence set forth in Table 4 and amino acid residues of the autophagy protein that are outside the amino acid sequence set forth in Table 4.

In some embodiments, the epitope is comprised in the amino acid sequence set forth in Table 4.

In some embodiments, the epitope is comprised in an amino acid sequence set forth in Table 3.

In some embodiments, the epitope is comprised in an amino acid sequence selected from the group consisting of a sequence set forth in Table 1.

In another embodiment, the isolated antibody specifically binds to the epitope that comprises the x residue in the amino acid sequence set forth in Table 4, wherein x is not phosphorylated.

In another embodiment, the isolated antibody specifically binds to the epitope that comprises the amino acid residue x in the amino acid sequence set forth in Table 4, wherein x is phosphorylated.

In another embodiment, the isolated antibody specifically binds to an epitope comprised in an amino acid sequence set forth in Table 4, wherein the x residue is not phosphorylated. The antibody does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated.

In another embodiment, the isolated antibody specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated. The antibody does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is not phosphorylated.

In another embodiment, the isolated antibody specifically binds to the full length autophagy protein at its natural conformation.

In another embodiment, the isolated antibody is a monoclonal or polyclonal antibody or antibody fragment.

In another embodiment, the complex is assessed by a format selected from the group consisting of an enzyme-linked immunosorbent assay (ELISA), immunoblotting, immunoprecipitation, radioimmunoassay (RIA), immunostaining, latex agglutination, indirect hemagglutination assay (IHA), complement fixation, indirect immunofluorescent assay (IFA), nephelometry, flow cytometry assay, plasmon resonance assay, chemiluminescence assay, lateral flow immunoassay, u-capture assay, inhibition assay and avidity assay.

In another embodiment, the complex is assessed in a homogeneous or a heterogeneous assay format.

Immunoassay

Although a variety of assay types are contemplated, the present methods frequently assess the complex formed between a full-length autophagy protein and the antibody via a sandwich or competitive assay format. On occasion, the complex is assessed in a homogeneous or a heterogeneous assay format. Also frequently, the complex is assessed by a format selected from the group consisting of an enzyme-linked immunosorbent assay (ELISA), immunoblotting, immunoprecipitation, radioimmunoassay (RIA), immunostaining, latex agglutination, indirect hemagglutination assay (IHA), complement fixation, indirect immunofluorescent assay (IFA), nephelometry, flow cytometry assay, plasmon resonance assay, chemiluminescence assay, lateral flow immunoassay, u-capture assay, inhibition assay and avidity assay.

In a sandwich assay format, the antibody that that specifically binds to an epitope that comprises the amino acid residue x in the amino acid sequence set forth in Table 4 is used as a first antibody. The antibody that is capable of binding to a portion of full-length autophagy protein other than a sequence set forth in Table 4, which binds to the first antibody, is used as a second antibody. Alternatively, in a sandwich assay, the antibody that that specifically binds to an epitope that comprises the amino acid residue x in an amino acid sequence set forth in Table 4 is used as a first antibody. The antibody that is capable of binding to a portion of whole autophagy polypeptide other than the sequence set forth in Table 4, which binds to the first antibody, is used as a second antibody.

Either the first antibody or the second antibody is frequently attached to a surface and functions as a capture antibody. The attachment can be direct or indirect. In a preferred embodiment, the attachment is provided via a biotin-avidin (or streptavidin) linking pair.

Determination of Phosphorylation Status

Phosphorylation site-specific binding molecules are disclosed that specifically bind at novel phosphorylation sites in various autophagy protein molecules set forth in Table 2. These molecules distinguish between the phosphorylated and unphosphorylated forms. In one embodiment, the binding molecule is an antibody or an antigen-binding fragment thereof. The antibody may specifically bind to an amino acid sequence comprising a phosphorylation site identified by “X” in each of the sequences set forth in Table 3.

In this aspect is a method to determine the phosphorylation status of an autophagy protein or fragment by detecting a polypeptide comprising the amino acid sequence set forth in Table 4. The method comprises contacting a sample containing or suspected of containing this protein with an isolated antibody that specifically binds to an epitope that comprises the x residue in the sequence set forth in Table 4. The antibody may recognize either the phosphorylated or nonphosphorylated form of this epitope, i.e., serine, threonine, tyrosine or phosphoserine, phosphoserine, or phosphotyrosine. The method further comprises a step of assessing a complex formed between the autophagy protein or fragment, if present in the sample, to determine the phosphorylation status of the autophagy protein.

An example of this embodiment involves using two antibodies, one that specifically recognizes serine and one that specifically recognizes phosphoserine. It can be appreciated that one of skill in the art can measure the phosphorylation status by determining the relative degree of staining of the two antibodies in various standards containing known amounts of phosphorylated and nonphosphorylated autophagy peptides to determine the phosphorylation status of an autophagy protein.

A further embodiment of this aspect is to determine the phosphorylation status of a full length autophagy protein. Optionally, this embodiment is used to determine the phosphorylation status of a full length autophagy protein in a biological sample. The biological sample may be a clinical sample. The determination of the phosphorylation status of an autophagy protein, or optionally a full length autophagy protein, in a biological sample may be conducted for the prognosis, diagnosis and/or treatment monitoring of a disease or disorder associated with abnormal phosphorylation status of a autophagy protein or fragment comprising an amino acid sequence set forth in Table 4.

Exemplary diseases associated with abnormal phosphorylation level of an autophagy protein or fragment may include ischemic brain injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, prion diseases and polyglutamine disorders including Huntington's disease and various spinocerebellar ataxias, transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease, breast cancer, ovarian cancer, brain cancer, pancreatic cancer, esophageal cancer, colorectal cancer, liver cancer, prostate cancer, renal cancer, lung cancer, Myocardial ischemia, cardiac remodeling, cardiomyopathy, hemodynamic stress, myocardial hypertrophy, Neuronal ceroid-lipofuscinosis (adult and juvenile), Multiple Sulfatase Deficiency (MSD) and Mucopolysaccharidosis type IIIA, Batten disease, Niemann-Pick C, Danon disease, Pompe disease, and dysfunction of innate and adaptive immunity against intracellular pathogens.

Method for Identifying a Phosphatase

Another aspect is a method for identifying a phosphatase that dephosphorylates an autophagy polypeptide on the x residue. The method comprises the following steps:

(1) providing an autophagy polypeptide comprising an amino acid sequence set forth in Table 1, wherein the x residue is phosphorylated, (2) contacting the autophagy polypeptide with a test protein and H₂O under conditions suitable for the dephosphorylation of the phosphoserine residue of the autophagy polypeptide; and (3) assessing the phosphorylation status of the autophagy polypeptide to determine whether the test protein is a phosphatase for the autophagy protein at the x residue.

In a further embodiment, the autophagy protein or fragment comprises an amino acid sequence set forth in Table 4 wherein the x residue is phosphorylated. Optionally, the phosphorylation status of the autophagy polypeptide is assessed by an isolated antibody that specifically binds to an epitope comprised in an amino acid sequence set forth in Table 4 wherein the x residue is not phosphorylated, but does not specifically bind to an epitope comprised of the same amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated. An example of this embodiment is the detection of a nonphosphorylated autophagy protein by detecting binding of an antibody that specifically binds to the nonphosphorylated epitope and does not bind to the phosphorylated epitope.

Method for Identifying a Phosphatase Modulator

Another aspect is a method for identifying a modulator of a phosphatase that dephosphorylates an autophagy protein on the x residue. The method comprises the following steps: (1) providing an autophagy polypeptide comprising an amino acid sequence selected from Table 1, wherein the x residue is phosphorylated; (2) contacting the autophagy polypeptide with a phosphatase that dephosphorylates the autophagy polypeptide on the x residue and H₂O under conditions suitable for the dephosphorylation of the phosphorylated x residue of the autophagy polypeptide in the presence or absence of a test substance; and (3) assessing and comparing dephosphorylation status of the autophagy polypeptide by the phosphatase to determine whether the test substance modulates the phosphatase.

In a further embodiment of this aspect, the autophagy protein or fragment comprises an amino acid sequence from Table 4 wherein the x residue is phosphorylated. Optionally, the phosphorylation status of the autophagy polypeptide is assessed by an isolated antibody that specifically binds to an epitope comprised in the amino acid sequence from Table 4, wherein the x residue is not phosphorylated, but does not specifically bind to an epitope comprised in the amino acid sequence from Table 4, wherein the x residue is phosphorylated.

Kit for Protein Detection

In another aspect is a kit for detecting an autophagy protein or fragment comprising an amino acid sequence from Table 4, wherein the x residue is either phosphorylated or nonphosphorylated, in a sample. The kit comprises, in a container, an isolated antibody that specifically binds to an epitope that comprises the amino acid residue x in the amino acid sequence from Table 4, wherein x is serine or phosphoserine.

An exemplary use of the kit is to specifically detect a native autophagy protein that is phosphorylated at the x residue. Another exemplary use of the kit is to specifically detect native autophagy protein that is not phosphorylated at the x residue.

Method of Treating Disease

The following aspect relates to a method of treating a disease or disorder associated with abnormal phosphorylation status of an autophagy protein or fragment comprising amino acid sequence from Table 4, wherein the x residue of serine, threonine, or tyrosine is phosphorylated or nonphosphorylated. The method comprises administering, to a subject when such a treatment is needed or desired, a sufficient amount of an isolated antibody that specifically binds to an epitope that comprises the amino acid residue x in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated or nonphosphorylated. The subject may be a mammal. The subject may be a human.

In some embodiments, the isolated antibody specifically binds to the full length autophagy protein at its natural conformation.

In some embodiments, the isolated antibody is a monoclonal or polyclonal antibody or antibody fragment.

Some embodiments further comprise the step of administering a pharmaceutically acceptable carrier and excipient.

In one embodiment of the above aspect the isolated antibody specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein x is not phosphorylated, but does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4, wherein x is phosphorylated. Optionally, the disease or disorder is associated with abnormal phosphorylation level of an autophagy protein or fragment, and the binding of the antibody to the autophagy protein or fragment prevents or reduces the phosphorylation level of the autophagy protein or fragment. As a further option, the diseases or disorders associated with abnormal phosphorylation level of an autophagy protein or fragment are ischemic brain injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, prion diseases and polyglutamine disorders including Huntington's disease and various spinocerebellar ataxias, transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease, breast cancer, ovarian cancer, brain cancer, pancreatic cancer, esophageal cancer, colorectal cancer, liver cancer, prostate cancer, renal cancer, lung cancer, Myocardial ischemia, cardiac remodeling, cardiomyopathy, hemodynamic stress, myocardial hypertrophy, Neuronal ceroid-lipofuscinosis (adult and juvenile), Multiple Sulfatase Deficiency (MSD) and Mucopolysaccharidosis type IIIA, Batten disease, Niemann-Pick C, Danon disease, Pompe disease, and dysfunction of innate and adaptive immunity against intracellular pathogens.

In another embodiment of the above aspect, the isolated antibody specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated, but does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is not phosphorylated. Optionally, the disease or disorder is associated with abnormally low phosphorylation level of an autophagy protein or fragment, and the binding of the antibody to the autophagy protein or fragment prevents or reduces dephosphorylation of the autophagy protein or fragment. As a further option, the disease or disorder associated with abnormally low phosphorylation level of an autophagy protein or fragment are ischemic brain injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, prion diseases and polyglutamine disorders including Huntington's disease and various spinocerebellar ataxias, transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease, breast cancer, ovarian cancer, brain cancer, pancreatic cancer, esophageal cancer, colorectal cancer, liver cancer, prostate cancer, renal cancer, lung cancer, Myocardial ischemia, cardiac remodeling, cardiomyopathy, hemodynamic stress, myocardial hypertrophy, Neuronal ceroid-lipofuscinosis (adult and juvenile), Multiple Sulfatase Deficiency (MSD) and Mucopolysaccharidosis type IIIA, Batten disease, Niemann-Pick C, Danon disease, Pompe disease, and dysfunction of innate and adaptive immunity against intracellular pathogens.

In another embodiment of the above aspect, the amino acid sequence of a sequence from Table 4 is comprised in a full length autophagy protein and the isolated antibody specifically binds to the full length autophagy protein. As a first option, the isolated antibody specifically binds to the full length autophagy protein when the x residue is not phosphorylated in the amino acid sequence set forth in Table 4, but does not specifically bind to the full length autophagy protein when the x residue is phosphorylated in the amino acid sequence set forth in Table 4. As a second option, the isolated antibody specifically binds to the full length autophagy protein when the x residue is phosphorylated in the amino acid sequence set forth in Table 4, but does not specifically bind to the full length autophagy protein when the x residue is not phosphorylated in the amino acid sequence set forth in Table 4.

Identification of a Kinase

Another aspect is a method for identifying a kinase that phosphorylates an autophagy protein on the phosphorylation site indicated by the x residue. The method comprises the steps of (1) providing an autophagy polypeptide comprising an amino acid sequence selected from Table 1, wherein the x residue is not phosophorylated; (2) contacting the autophagy polypeptide with a test protein and ATP under conditions suitable for the phosphorylation of the serine residue of the autophagy polypeptide; and (3) assessing the phosphorylation status of the autophagy polypeptide to determine whether the test protein is a kinase for the autophagy protein on the x residue.

In another embodiment of this aspect, the autophagy protein or fragment comprises an amino acid sequence set forth in Table 4 wherein the x residue is not phosphorylated.

In another embodiment, the phosphorylation status of the autophagy polypeptide is assessed by an isolated antibody that specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated, but does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is not phosphorylated.

Identification of a Kinase Modulator

Another aspect is a method for identifying a modulator of a kinase that phosphorylates an autophagy protein on the x residue. The method comprises the steps of: (1) providing an autophagy polypeptide comprising an amino acid sequence selected from Table 1, wherein x is not phosphorylated; (2) contacting the autophagy polypeptide with a kinase that phosphorylates the autophagy polypeptide on the x residue and ATP under conditions suitable for the phosphorylation of the x residue of the autophagy polypeptide in the presence or absence of a test substance; and (3) assessing and comparing phosphorylation status of the autophagy polypeptide by the kinase to determine whether the test substance modulates the kinase.

In one embodiment of this aspect, the autophagy protein or fragment comprises an amino acid sequence set forth in Table 4, wherein x is serine.

In another embodiment of this aspect, the phosphorylation status of the autophagy polypeptide is assessed by an isolated antibody that specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated, but does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4, wherein x is not phosphorylated.

Isolated Nucleic Acid Fragment

Another aspect is an isolated nucleic acid fragment which is comprised of a sequence of nucleotides encoding an autophagy peptide comprising an amino acid sequence selected from Table 1, wherein x is not phosphorylated. The autophagy peptide is not a full-length autophagy protein comprising an amino acid sequence set forth in Table 2. The nucleic acid may be DNA. The nucleic acid may also be RNA.

In another embodiment, the autophagy peptide comprises an amino acid sequence set forth in Table 4.

In another embodiment there is a plasmid which comprises the nucleic acid fragments of this aspect.

In another embodiment there is a vector which comprises the nucleic acid fragments of this aspect.

In another embodiment, there may be a cell which comprises the plasmids or vectors of this aspect. The cell may be a bacterial cell, a yeast cell, a fungal cell, a plant cell, an insect cell, an animal cell or a human cell. The cell may be used in a method for producing an autophagy peptide, comprising growing the cell of claim 112 under conditions whereby the autophagy peptide is expressed by the cell, and recovering the expressed autophagy peptide. Optionally, the method further comprises a step of phosphorylating the autophagy peptide at the x residue (as indicated in Tables 4 and 5).

Screening for Compounds

In another aspect is a method for identifying a compound that binds to specifically to an autophagy polypeptide phosphorylated at the x residue. The method comprises the following steps: 1) providing a phosphorylated autophagy polypeptide comprising an amino acid sequence selected from Table 1, wherein the x residue is phosphorylated; 2) contacting the phosphorylated autophagy polypeptide with a test compound and H₂O under conditions suitable for binding of the test protein with the autophagy polypeptide; 3) assessing binding of the phosphorylated autophagy polypeptide with the test compound; 4) providing a nonphosphorylated autophagy polypeptide comprising an amino acid sequence selected from Table 1, wherein the x residue is phosphorylated; 5) contacting the nonphosphorylated autophagy polypeptide with a test compound and H₂O under conditions suitable for binding of the test protein with the autophagy polypeptide; and 6) assessing binding of the nonphosphorylated autophagy polypeptide with the test compound. In the method, the compound that binds specifically to a phosphorylated autophagy polypeptide is a test compound which binds to phosphorylated autophagy polypeptide according to step 3 but does not bind to nonphosphorylated autophagy polypeptide according to step 5. In some embodiments, the test compound may be a polypeptide. In some embodiments, the test compound may be a peptide. In some embodiments the test compound may be a nucleic acid. In some embodiments, the compound may be a small molecule.

In another aspect is a method for identifying a compound that binds to specifically to an autophagy polypeptide that is not phosphorylated at the x residue. The method comprises the following steps: 1) providing a nonphosphorylated autophagy polypeptide comprising an amino acid sequence selected from Table 1, wherein x is serine; 2) contacting the nonphosphorylated autophagy polypeptide with a test compound and H₂O under conditions suitable for binding of the test protein with the autophagy polypeptide; 3) assessing binding of the nonphosphorylated autophagy polypeptide with the test compound; 4) providing a phosphorylated autophagy polypeptide comprising an amino acid sequence selected from Table 1, wherein the x residue is phosphorylated; 5) contacting the phosphorylated autophagy polypeptide with a test compound and H₂O under conditions suitable for binding of the test protein with the autophagy polypeptide; and 6) assessing binding of the phosphorylated autophagy polypeptide with the test compound. In the method, the compound that binds specifically to a nonphosphorylated autophagy polypeptide is a test compound which binds to nonphosphorylated autophagy polypeptide according to step 3, but does not bind to the phosphorylated autophagy polypeptide according to step 5. In some embodiments, the test compound may be a polypeptide. In some embodiments, the test compound may be a peptide. In some embodiments the test compound may be a nucleic acid. In some embodiments, the compound may be a small molecule.

Method of Treating Disease by Modulating Phosphorylation of an Autophagy Polypeptide

Diseases may be treated by modulating the phosphorylation of an autophagy polypeptide. These diseases may arise from abnormal phosphorylation of the autophagy polypeptide. Alternatively, the phosphorylation status of an autophagy polypeptide may be normal, but the disease may be treated by modulating the phosphorylation of an autophagy polypeptide to enhance or reduce autophagy. Such exemplary diseases include ischemic brain injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, prion diseases and polyglutamine disorders including Huntington's disease and various spinocerebellar ataxias, transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease, breast cancer, ovarian cancer, brain cancer, pancreatic cancer, esophageal cancer, colorectal cancer, liver cancer, prostate cancer, renal cancer, lung cancer, Myocardial ischemia, cardiac remodeling, cardiomyopathy, hemodynamic stress, myocardial hypertrophy, Neuronal ceroid-lipofuscinosis (adult and juvenile), Multiple Sulfatase Deficiency (MSD) and Mucopolysaccharidosis type IIIA, Batten disease, Niemann-Pick C, Danon disease, Pompe disease, and dysfunction of innate and adaptive immunity against intracellular pathogens.

By increasing the rate of autophagy, there can be enhanced cleaning and turnover of damaged organelles, protein aggregates, and other unwanted cellular features that can be removed by autophagy. By decreasing the rate of autophagy, a diseased cell, such as a cancer cell, may be more susceptible to treatment by chemotherapeutic and other agents.

Autophagy polypeptide phosphorylation may be increased in order to increase autophagy.

Alternatively, autophagy polypeptide phosphorylation may be decreased in order to decrease autophagy.

Autophagy polypeptide phosphorylation may be decreased in order to increase autophagy.

Alternatively, autophagy polypeptide phosphorylation may be increased in order to decrease autophagy.

Antibody Microarrays

In another aspect is a microarray comprising an antibody disclosed above. Microarrays are useful for screening potential binding partners for binding to proteins on an array, in a high-throughput manner. Microarrays are typically comprised of a large number of a library of target or capture reagents robotically arrayed or spotted in high density onto a solid support. Potential binding partners for screening are labeled, usually with fluorescence, and contacted with to a target or capture reagent immobilized on the array under conditions to allow for binding. Following a wash step, binding to the individual targets may be measured and quantified. Each collection of binding partners may be tested individually, with results from individual arrays compared.

An antibody microarray using antibodies of the present invention has substantial utility. The microarray may be used as a diagnostic tool to monitor the phosphorylation of autophagy proteins in a variety of tissue samples from a patient in order to determine whether the patient has a disease that is correlated with an abnormal degree of autophagy. Additionally, the microarray may be used to screen for drugs and other compounds that affect the phosphorylation status of autophagy proteins.

Example 1 Production of an APG3L Tyrosine-18 Phosphospecific Polyclonal Antibody

A 12 amino acid phospho-peptide antigen, LEVAEY*LTPVLC (where Y*=phosphotyrosine) (SEQ ID NO: 2), corresponding to residues 13-23 of human APG3L plus cysteine on the C-terminal for coupling, was constructed according to standard synthesis techniques using a Rainin/Protein Technologies, Inc., Symphony peptide synthesizer. See, e.g., Antibodies: A Laboratory Manual, Chapter 5, pages 75-76, Harlow & Lane Eds., Cold Spring Harbor Laboratory (1988); Czernik, Methods In Enzymology (1991) 201:264-283; Merrifield, J. Am. Chem. Soc. (1962) 85:21-49.

This peptide was coupled to KLH, and rabbits were injected intradermally (ID) on the back with antigen in complete Freunds adjuvant (200 μg antigen per rabbit). The rabbits were boosted with same antigen in incomplete Freund adjuvant (100 μg antigen per rabbit) weekly for eight. Coincident with the dates of the third through eighth boosts, 15-20 mL bleed per rabbit was collected. One week after the eight boost, a terminating bleed of 40-60 mL per rabbit was collected. The sera were purified by Protein A-affinity chromatography as previously described (see Antibodies: A Laboratory Manual, Cold Spring Harbor, supra.). The eluted immunoglobulins were further loaded onto LEVAEYLTPVLC (SEQ ID NO: 3)-resin Knotes column. The flow through fraction was collected and applied onto LEVAEY*LTPVLC (SEQ ID NO: 2)-resin column. After washing the column extensively, the phospho-APG3L-Y18 antibodies were eluted and kept in antibody storage buffer.

The antibody was confirmed for phosphospecificity against the peptide antigen using Dot blot assay. 50 ng of phosphopeptide and 50 ng of the nonphosphorylated version of the peptide were spotted separately onto a nitrocellulose membrane. The membrane was allowed to dry. Non-specific sites were blocked by soaking in 5% BSA in TBS-T (0.5-1 hr, RT). A 10 cm petri dish was used for the reaction chamber. The membrane was incubated with the purified APG3L-Y18 phosphospecific polyclonal antibody at a concentration of 0.5 μg/mL dissolved in BSA/TBS-T for 30 min at room temperature. The membrane was washed three times with TBS-T (3×5 min). The membrane was incubated with secondary antibody conjugated to HRP using manufacturer's recommended dilution for 30 min at room temperature. The membrane was then washed three times with TBS-T (15 min×1, 5 min×2), then once with TBS (5 min). The membrane was then incubated with ECL reagent for 1 min, covered with Saran-wrap after removing excess solution from the surface, and then exposed to X-ray film in a dark room at several different lengths of exposure. The results of the dot blot is shown in FIG. 1. As shown in this Figure, the antibody, as expected, only recognized the phosphorylated peptide. It did not recognize the non-phosphorylated peptide.

Example 2 Production of an APG4A Serine-100 Phosphospecific Polyclonal Antibody

A 12 amino acid phospho-peptide antigen, LGRDWS*WEKQKC (SEQ ID NO: 4) (where S*=phosphoserine), corresponding to residues 95-105 of human APG4A plus cysteine on the C-terminal for coupling, was constructed according to standard synthesis techniques using a Rainin/Protein Technologies, Inc., Symphony peptide synthesizer. See, e.g., Antibodies: A Laboratory Manual, Chapter 5, pages 75-76, Harlow & Lane Eds., Cold Spring Harbor Laboratory (1988); Czernik, Methods In Enzymology (1991) 201:264-283; Merrifield, J. Am. Chem. Soc. (1962) 85:21-49.

This peptide was coupled to KLH, and rabbits were injected intradermally (ID) on the back with antigen in complete Freunds adjuvant (200 μg antigen per rabbit). The rabbits were boosted with same antigen in incomplete Freund adjuvant (100 μg antigen per rabbit) weekly for eight. Coincident with the dates of the third through eighth boosts, 15-20 mL bleed per rabbit was collected. One week after the eight boost, a terminating bleed of 40-60 mL per rabbit was collected. The sera were purified by Protein A-affinity chromatography as previously described (see Antibodies: A Laboratory Manual, Cold Spring Harbor, supra.). The eluted immunoglobulins were further loaded onto LGRDWSWEKQKC (SEQ ID NO: 5)-resin Knotes column. The flow through fraction was collected and applied onto LGRDWS*WEKQKC (SEQ ID NO: 4)-resin column. After washing the column extensively, the phospho-APG4A-S100 antibodies were eluted and kept in antibody storage buffer.

The antibody was confirmed for phosphospecificity against the peptide antigen using Dot blot assay. 50 ng of phosphopeptide and 50 ng of the nonphosphorylated version of the peptide were spotted separately onto a nitrocellulose membrane. The membrane was allowed to dry. Non-specific sites were blocked by soaking in 5% BSA in TBS-T (0.5-1 hr, RT). A 10 cm petri dish was used for the reaction chamber. The membrane was incubated with the purified APG4A-S100 phosphospecific polyclonal antibody at a concentration of 0.5 μg/mL dissolved in BSA/TBS-T for 30 min at room temperature. The membrane was washed three times with TBS-T (3×5 min). The membrane was incubated with secondary antibody conjugated to HRP using manufacturer's recommended dilution for 30 min at room temperature. The membrane was then washed three times with TBS-T (15 min×1, 5 min×2), then once with TBS (5 min). The membrane was then incubated with ECL reagent for 1 min, covered with Saran-wrap after removing excess solution from the surface, and then exposed to X-ray film in a dark room at several different lengths of exposure. The results of the dot blot is shown in FIG. 2. As shown in this Figure, the antibody, as expected, only recognized the phosphorylated peptide. It did not recognize the non-phosphorylated peptide.

Example 3 Production of an APG4C Serine-166 Phosphospecific Polyclonal Antibody

A 12 amino acid phospho-peptide antigen, FEASLS*GEREFC (SEQ ID NO: 6) (where S*=phosphoserine), corresponding to residues 161-171 of human APG4C plus cysteine on the C-terminal for coupling, was constructed according to standard synthesis techniques using a Rainin/Protein Technologies, Inc., Symphony peptide synthesizer. See, e.g., Antibodies: A Laboratory Manual, Chapter 5, pages 75-76, Harlow & Lane Eds., Cold Spring Harbor Laboratory (1988); Czernik, Methods In Enzymology (1991) 201:264-283; Merrifield, J. Am. Chem. Soc. (1962) 85:21-49.

This peptide was coupled to KLH, and rabbits were injected intradermally (ID) on the back with antigen in complete Freunds adjuvant (200 μg antigen per rabbit). The rabbits were boosted with same antigen in incomplete Freund adjuvant (100 μg antigen per rabbit) weekly for eight. Coincident with the dates of the third through eighth boosts, 15-20 mL bleed per rabbit was collected. One week after the eight boost, a terminating bleed of 40-60 mL per rabbit was collected. The sera were purified by Protein A-affinity chromatography as previously described (see Antibodies: A Laboratory Manual, Cold Spring Harbor, supra.). The eluted immunoglobulins were further loaded onto FEASLSGEREFC (SEQ ID NO: 7)-resin Knotes column. The flow through fraction was collected and applied onto FEASLS*GEREFC (SEQ ID NO: 6)-resin column. After washing the column extensively, the phospho-APG4C-S166 antibodies were eluted and kept in antibody storage buffer.

The antibody was confirmed for phosphospecificity against the peptide antigen using Dot blot assay. 50 ng of phosphopeptide and 50 ng of the nonphosphorylated version of the peptide were spotted separately onto a nitrocellulose membrane. The membrane was allowed to dry. Non-specific sites were blocked by soaking in 5% BSA in TBS-T (0.5-1 hr, RT). A 10 cm petri dish was used for the reaction chamber. The membrane was incubated with the purified APG4C-S166 phosphospecific polyclonal antibody at a concentration of 0.5 μg/mL dissolved in BSA/TBS-T for 30 min at room temperature. The membrane was washed three times with TBS-T (3×5 min). The membrane was incubated with secondary antibody conjugated to HRP using manufacturer's recommended dilution for 30 min at room temperature. The membrane was then washed three times with TBS-T (15 min×1, 5 min×2), then once with TBS (5 min). The membrane was then incubated with ECL reagent for 1 min, covered with Saran-wrap after removing excess solution from the surface, and then exposed to X-ray film in a dark room at several different lengths of exposure. The results of the dot blot is shown in FIG. 3. As shown in this Figure, the antibody, as expected, only recognized the phosphorylated peptide. It did not recognize the non-phosphorylated peptide.

Example 4 Production of an APG4C Serine-177 Phosphospecific Polyclonal Antibody

A 12 amino acid phospho-peptide antigen, KTPTIS*LKETIC (SEQ ID NO: 8) (where S*=phosphoserine), corresponding to residues 172-182 of human APG4C plus cysteine on the C-terminal for coupling, was constructed according to standard synthesis techniques using a Rainin/Protein Technologies, Inc., Symphony peptide synthesizer. See, e.g., Antibodies: A Laboratory Manual, Chapter 5, pages 75-76, Harlow & Lane Eds., Cold Spring Harbor Laboratory (1988); Czernik, Methods In Enzymology (1991) 201:264-283; Merrifield, J. Am. Chem. Soc. (1962) 85:21-49.

This peptide was coupled to KLH, and rabbits were injected intradermally (ID) on the back with antigen in complete Freunds adjuvant (200 μg antigen per rabbit). The rabbits were boosted with same antigen in incomplete Freund adjuvant (100 μg antigen per rabbit) weekly for eight. Coincident with the dates of the third through eighth boosts, 15-20 mL bleed per rabbit was collected. One week after the eight boost, a terminating bleed of 40-60 mL per rabbit was collected. The sera were purified by Protein A-affinity chromatography as previously described (see Antibodies: A Laboratory Manual, Cold Spring Harbor, supra.). The eluted immunoglobulins were further loaded onto KTPTISLKETIC (SEQ ID NO: 9)-resin Knotes column. The flow through fraction was collected and applied onto KTPTIS*LKETIC (SEQ ID NO: 8)-resin column. After washing the column extensively, the phospho-APG4C-S177 antibodies were eluted and kept in antibody storage buffer.

The antibody was confirmed for phosphospecificity against the peptide antigen using Dot blot assay. 50 ng of phosphopeptide and 50 ng of the nonphosphorylated version of the peptide were spotted separately onto a nitrocellulose membrane. The membrane was allowed to dry. Non-specific sites were blocked by soaking in 5% BSA in TBS-T (0.5-1 hr, RT). A 10 cm petri dish was used for the reaction chamber. The membrane was incubated with the purified APG4C-S177 phosphospecific polyclonal antibody at a concentration of 0.5 μg/mL dissolved in BSA/TBS-T for 30 min at room temperature. The membrane was washed three times with TBS-T (3×5 min). The membrane was incubated with secondary antibody conjugated to HRP using manufacturer's recommended dilution for 30 min at room temperature. The membrane was then washed three times with TBS-T (15 min×1, 5 min×2), then once with TBS (5 min). The membrane was then incubated with ECL reagent for 1 min, covered with Saran-wrap after removing excess solution from the surface, and then exposed to X-ray film in a dark room at several different lengths of exposure. The results of the dot blot is shown in FIG. 4. As shown in this Figure, the antibody, as expected, only recognized the phosphorylated peptide. It did not recognize the non-phosphorylated peptide.

Example 5 Production of an APG4C Serine-398 Phosphospecific Polyclonal Antibody

A 12 amino acid phospho-peptide antigen, CDFKRAS*EEITK (SEQ ID NO: 10) (where S*=phosphoserine), corresponding to residues 393-403 of human APG4C plus cysteine on the N-terminal for coupling, was constructed according to standard synthesis techniques using a Rainin/Protein Technologies, Inc., Symphony peptide synthesizer. See, e.g., Antibodies: A Laboratory Manual, Chapter 5, pages 75-76, Harlow & Lane Eds., Cold Spring Harbor Laboratory (1988); Czernik, Methods In Enzymology (1991) 201:264-283; Merrifield, J. Am. Chem. Soc. (1962) 85:21-49.

This peptide was coupled to KLH, and rabbits were injected intradermally (ID) on the back with antigen in complete Freunds adjuvant (200 μg antigen per rabbit). The rabbits were boosted with same antigen in incomplete Freund adjuvant (100 μg antigen per rabbit) weekly for eight. Coincident with the dates of the third through eighth boosts, 15-20 mL bleed per rabbit was collected. One week after the eight boost, a terminating bleed of 40-60 mL per rabbit was collected. The sera were purified by Protein A-affinity chromatography as previously described (see Antibodies: A Laboratory Manual, Cold Spring Harbor, supra.). The eluted immunoglobulins were further loaded onto CDFKRASEEITK (SEQ ID NO: 11)-resin Knotes column. The flow through fraction was collected and applied onto CDFKRAS*EEITK (SEQ ID NO: 10)-resin column. After washing the column extensively, the phospho-APG4C-5398 antibodies were eluted and kept in antibody storage buffer.

The antibody was confirmed for phosphospecificity against the peptide antigen using Dot blot assay. 50 ng of phosphopeptide and 50 ng of the nonphosphorylated version of the peptide were spotted separately onto a nitrocellulose membrane. The membrane was allowed to dry. Non-specific sites were blocked by soaking in 5% BSA in TBS-T (0.5-1 hr, RT). A 10 cm petri dish was used for the reaction chamber. The membrane was incubated with the purified APG4C-5398 phosphospecific polyclonal antibody at a concentration of 0.5 μg/mL dissolved in BSA/TBS-T for 30 min at room temperature. The membrane was washed three times with TBS-T (3×5 min). The membrane was incubated with secondary antibody conjugated to HRP using manufacturer's recommended dilution for 30 min at room temperature. The membrane was then washed three times with TBS-T (15 min×1, 5 min×2), then once with TBS (5 min). The membrane was then incubated with ECL reagent for 1 min, covered with Saran-wrap after removing excess solution from the surface, and then exposed to X-ray film in a dark room at several different lengths of exposure. The results of the dot blot is shown in FIG. 5. As shown in this Figure, the antibody, as expected, only recognized the phosphorylated peptide. It did not recognize the non-phosphorylated peptide.

Example 6 Production of an APG4C Serine-451 Phosphospecific Polyclonal Antibody

A 12 amino acid phospho-peptide antigen, CQLKRFS*TEEFV (SEQ ID NO: 12) (where S*=phosphoserine), corresponding to residues 446-456 of human APG4C plus cysteine on the N-terminal for coupling, was constructed according to standard synthesis techniques using a Rainin/Protein Technologies, Inc., Symphony peptide synthesizer. See, e.g., Antibodies: A Laboratory Manual, Chapter 5, pages 75-76, Harlow & Lane Eds., Cold Spring Harbor Laboratory (1988); Czernik, Methods In Enzymology (1991) 201:264-283; Merrifield, J. Am. Chem. Soc. (1962) 85:21-49.

This peptide was coupled to KLH, and rabbits were injected intradermally (ID) on the back with antigen in complete Freunds adjuvant (200 μg antigen per rabbit). The rabbits were boosted with same antigen in incomplete Freund adjuvant (100 μg antigen per rabbit) weekly for eight. Coincident with the dates of the third through eighth boosts, 15-20 mL bleed per rabbit was collected. One week after the eight boost, a terminating bleed of 40-60 mL per rabbit was collected. The sera were purified by Protein A-affinity chromatography as previously described (see Antibodies: A Laboratory Manual, Cold Spring Harbor, supra.). The eluted immunoglobulins were further loaded onto CQLKRFSTEEFV (SEQ ID NO: 13)-resin Knotes column. The flow through fraction was collected and applied onto CQLKRFS*TEEFV (SEQ ID NO: 12)-resin column. After washing the column extensively, the phospho-APG4C-5451 antibodies were eluted and kept in antibody storage buffer.

The antibody was confirmed for phosphospecificity against the peptide antigen using Dot blot assay. 50 ng of phosphopeptide and 50 ng of the nonphosphorylated version of the peptide were spotted separately onto a nitrocellulose membrane. The membrane was allowed to dry. Non-specific sites were blocked by soaking in 5% BSA in TBS-T (0.5-1 hr, RT). A 10 cm petri dish was used for the reaction chamber. The membrane was incubated with the purified APG4C-S451 phosphospecific polyclonal antibody at a concentration of 0.5 μg/mL dissolved in BSA/TBS-T for 30 min at room temperature. The membrane was washed three times with TBS-T (3×5 min). The membrane was incubated with secondary antibody conjugated to HRP using manufacturer's recommended dilution for 30 min at room temperature. The membrane was then washed three times with TBS-T (15 min×1, 5 min×2), then once with TBS (5 min). The membrane was then incubated with ECL reagent for 1 min, covered with Saran-wrap after removing excess solution from the surface, and then exposed to X-ray film in a dark room at several different lengths of exposure. The results of the dot blot is shown in FIG. 6. As shown in this Figure, the antibody, as expected, only recognized the phosphorylated peptide. It did not recognize the non-phosphorylated peptide.

Example 7 Production of an APG4D Serine-15 Phosphospecific Polyclonal Antibody

A 12 amino acid phospho-peptide antigen, QYRSSS*PEDARC (SEQ ID NO: 14) (where S*=phosphoserine), corresponding to residues 10-20 of human APG4D (SEQ ID NO:196) plus cysteine on the C-terminal for coupling, was constructed according to standard synthesis techniques using a Rainin/Protein Technologies, Inc., Symphony peptide synthesizer. See, e.g., Antibodies: A Laboratory Manual, Chapter 5, pages 75-76, Harlow & Lane Eds., Cold Spring Harbor Laboratory (1988); Czernik, Methods In Enzymology (1991) 201:264-283; Merrifield, J. Am. Chem. Soc. (1962) 85:21-49.

This peptide was coupled to KLH, and rabbits were injected intradermally (ID) on the back with antigen in complete Freunds adjuvant (200 μg antigen per rabbit). The rabbits were boosted with same antigen in incomplete Freund adjuvant (100 μg antigen per rabbit) weekly for eight. Coincident with the dates of the third through eighth boosts, 15-20 mL bleed per rabbit was collected. One week after the eight boost, a terminating bleed of 40-60 mL per rabbit was collected. The sera were purified by Protein A-affinity chromatography as previously described (see Antibodies: A Laboratory Manual, Cold Spring Harbor, supra.). The eluted immunoglobulins were further loaded onto QYRSSSPEDARC (SEQ ID NO: 15)-resin Knotes column. The flow through fraction was collected and applied onto QYRSSS*PEDARC (SEQ ID NO: 14)-resin column. After washing the column extensively, the phospho-APG4D-S15 antibodies were eluted and kept in antibody storage buffer.

The antibody was confirmed for phosphospecificity against the peptide antigen using Dot blot assay. 50 ng of phosphopeptide and 50 ng of the nonphosphorylated version of the peptide were spotted separately onto a nitrocellulose membrane. The membrane was allowed to dry. Non-specific sites were blocked by soaking in 5% BSA in TBS-T (0.5-1 hr, RT). A 10 cm petri dish was used for the reaction chamber. The membrane was incubated with the purified APG4D-S15 phosphospecific polyclonal antibody at a concentration of 0.5 μg/mL dissolved in BSA/TBS-T for 30 min at room temperature. The membrane was washed three times with TBS-T (3×5 min). The membrane was incubated with secondary antibody conjugated to HRP using manufacturer's recommended dilution for 30 min at room temperature. The membrane was then washed three times with TBS-T (15 min×1, 5 min×2), then once with TBS (5 min). The membrane was then incubated with ECL reagent for 1 min, covered with Saran-wrap after removing excess solution from the surface, and then exposed to X-ray film in a dark room at several different lengths of exposure. The results of the dot blot is shown in FIG. 7. As shown in this Figure, the antibody, as expected, only recognized the phosphorylated peptide. It did not recognize the non-phosphorylated peptide.

Example 8 Production of an APG4D Serine-341 Phosphospecific Polyclonal Antibody

A 12 amino acid phospho-peptide antigen, CGKPRHS*LYFIG (SEQ ID NO: 16) (where S*=phosphoserine), corresponding to residues 336-346 of human APG4D plus cysteine on the N-terminal for coupling, was constructed according to standard synthesis techniques using a Rainin/Protein Technologies, Inc., Symphony peptide synthesizer. See, e.g., Antibodies: A Laboratory Manual, Chapter 5, pages 75-76, Harlow & Lane Eds., Cold Spring Harbor Laboratory (1988); Czernik, Methods In Enzymology (1991) 201:264-283; Merrifield, J. Am. Chem. Soc. (1962) 85:21-49.

This peptide was coupled to KLH, and rabbits were injected intradermally (ID) on the back with antigen in complete Freunds adjuvant (200 μg antigen per rabbit). The rabbits were boosted with same antigen in incomplete Freund adjuvant (100 μg antigen per rabbit) weekly for eight. Coincident with the dates of the third through eighth boosts, 15-20 mL bleed per rabbit was collected. One week after the eight boost, a terminating bleed of 40-60 mL per rabbit was collected. The sera were purified by Protein A-affinity chromatography as previously described (see Antibodies: A Laboratory Manual, Cold Spring Harbor, supra.). The eluted immunoglobulins were further loaded onto CGKPRHSLYFIG (SEQ ID NO: 17)-resin Knotes column. The flow through fraction was collected and applied onto CGKPRHS*LYFIG (SEQ ID NO: 16)-resin column. After washing the column extensively, the phospho-APG4D-5341 antibodies were eluted and kept in antibody storage buffer.

The antibody was confirmed for phosphospecificity against the peptide antigen using Dot blot assay. 50 ng of phosphopeptide and 50 ng of the nonphosphorylated version of the peptide were spotted separately onto a nitrocellulose membrane. The membrane was allowed to dry. Non-specific sites were blocked by soaking in 5% BSA in TBS-T (0.5-1 hr, RT). A 10 cm petri dish was used for the reaction chamber. The membrane was incubated with the purified APG4D-5341 phosphospecific polyclonal antibody at a concentration of 0.5 μg/mL dissolved in BSA/TBS-T for 30 min at room temperature. The membrane was washed three times with TBS-T (3×5 min). The membrane was incubated with secondary antibody conjugated to HRP using manufacturer's recommended dilution for 30 min at room temperature. The membrane was then washed three times with TBS-T (15 min×1, 5 min×2), then once with TBS (5 min). The membrane was then incubated with ECL reagent for 1 min, covered with Saran-wrap after removing excess solution from the surface, and then exposed to X-ray film in a dark room at several different lengths of exposure. The results of the dot blot is shown in FIG. 8. As shown in this Figure, the antibody, as expected, only recognized the phosphorylated peptide. It did not recognize the non-phosphorylated peptide.

Example 9 Production of an APG4D Serine-467 Phosphospecific Polyclonal Antibody

A 12 amino acid phospho-peptide antigen, CRAKRPS*SEDFV (SEQ ID NO: 18) (where S*=phosphoserine), corresponding to residues 462-472 of human APG4D plus cysteine on the N-terminal for coupling, was constructed according to standard synthesis techniques using a Rainin/Protein Technologies, Inc., Symphony peptide synthesizer. See, e.g., Antibodies: A Laboratory Manual, Chapter 5, pages 75-76, Harlow & Lane Eds., Cold Spring Harbor Laboratory (1988); Czernik, Methods In Enzymology (1991) 201:264-283; Merrifield, J. Am. Chem. Soc. (1962) 85:21-49.

This peptide was coupled to KLH, and rabbits were injected intradermally (ID) on the back with antigen in complete Freunds adjuvant (200 μg antigen per rabbit). The rabbits were boosted with same antigen in incomplete Freund adjuvant (100 μg antigen per rabbit) weekly for eight. Coincident with the dates of the third through eighth boosts, 15-20 mL bleed per rabbit was collected. One week after the eight boost, a terminating bleed of 40-60 mL per rabbit was collected. The sera were purified by Protein A-affinity chromatography as previously described (see Antibodies: A Laboratory Manual, Cold Spring Harbor, supra.). The eluted immunoglobulins were further loaded onto CRAKRPSSEDFV (SEQ ID NO: 19)-resin Knotes column. The flow through fraction was collected and applied onto CRAKRPS*SEDFV (SEQ ID NO: 18)-resin column. After washing the column extensively, the phospho-APG4D-5467 antibodies were eluted and kept in antibody storage buffer.

The antibody was confirmed for phosphospecificity against the peptide antigen using Dot blot assay. 50 ng of phosphopeptide and 50 ng of the nonphosphorylated version of the peptide were spotted separately onto a nitrocellulose membrane. The membrane was allowed to dry. Non-specific sites were blocked by soaking in 5% BSA in TBS-T (0.5-1 hr, RT). A 10 cm petri dish was used for the reaction chamber. The membrane was incubated with the purified APG4D-5467 phosphospecific polyclonal antibody at a concentration of 0.5 μg/mL dissolved in BSA/TBS-T for 30 min at room temperature. The membrane was washed three times with TBS-T (3×5 min). The membrane was incubated with secondary antibody conjugated to HRP using manufacturer's recommended dilution for 30 min at room temperature. The membrane was then washed three times with TBS-T (15 min×1, 5 min×2), then once with TBS (5 min). The membrane was then incubated with ECL reagent for 1 min, covered with Saran-wrap after removing excess solution from the surface, and then exposed to X-ray film in a dark room at several different lengths of exposure. The results of the dot blot is shown in FIG. 9. As shown in this Figure, the antibody, as expected, only recognized the phosphorylated peptide. It did not recognize the non-phosphorylated peptide.

Example 10 Production of an APG7L Serine-95 Phosphospecific Polyclonal Antibody

A 12 amino acid phospho-peptide antigen, TNTLES*FKTADC (SEQ ID NO: 20) (where S*=phosphoserine), corresponding to residues 90-100 of human APG7L plus cysteine on the C-terminal for coupling, was constructed according to standard synthesis techniques using a Rainin/Protein Technologies, Inc., Symphony peptide synthesizer. See, e.g., Antibodies: A Laboratory Manual, Chapter 5, pages 75-76, Harlow & Lane Eds., Cold Spring Harbor Laboratory (1988); Czernik, Methods In Enzymology (1991) 201:264-283; Merrifield, J. Am. Chem. Soc. (1962) 85:21-49.

This peptide was coupled to KLH, and rabbits were injected intradermally (ID) on the back with antigen in complete Freunds adjuvant (200 μg antigen per rabbit). The rabbits were boosted with same antigen in incomplete Freund adjuvant (100 μg antigen per rabbit) weekly for eight. Coincident with the dates of the third through eighth boosts, 15-20 mL bleed per rabbit was collected. One week after the eight boost, a terminating bleed of 40-60 mL per rabbit was collected. The sera were purified by Protein A-affinity chromatography as previously described (see Antibodies: A Laboratory Manual, Cold Spring Harbor, supra.). The eluted immunoglobulins were further loaded onto TNTLESFKTADC (SEQ ID NO: 21)-resin Knotes column. The flow through fraction was collected and applied onto TNTLES*FKTADC (SEQ ID NO: 20)-resin column. After washing the column extensively, the phospho-APG7-S95 antibodies were eluted and kept in antibody storage buffer.

The antibody was confirmed for phosphospecificity against the peptide antigen using Dot blot assay. 50 ng of phosphopeptide and 50 ng of the nonphosphorylated version of the peptide were spotted separately onto a nitrocellulose membrane. The membrane was allowed to dry. Non-specific sites were blocked by soaking in 5% BSA in TBS-T (0.5-1 hr, RT). A 10 cm petri dish was used for the reaction chamber. The membrane was incubated with the purified APG7-S95 phosphospecific polyclonal antibody at a concentration of 0.5 μg/mL dissolved in BSA/TBS-T for 30 min at room temperature. The membrane was washed three times with TBS-T (3×5 min). The membrane was incubated with secondary antibody conjugated to HRP using manufacturer's recommended dilution for 30 min at room temperature. The membrane was then washed three times with TBS-T (15 min×1, 5 min×2), then once with TBS (5 min). The membrane was then incubated with ECL reagent for 1 min, covered with Saran-wrap after removing excess solution from the surface, and then exposed to X-ray film in a dark room at several different lengths of exposure. The results of the dot blot is shown in FIG. 10. As shown in this Figure, the antibody, as expected, only recognized the phosphorylated peptide. It did not recognize the non-phosphorylated peptide.

Example 11 Production of an APG9L1 Serine-735 Phosphospecific Polyclonal Antibody

A 12 amino acid phospho-peptide antigen, WHRRES*DESGEC (SEQ ID NO: 22) (where S*=phosphoserine), corresponding to residues 730-740 of human APG9L1 plus cysteine on the C-terminal for coupling, was constructed according to standard synthesis techniques using a Rainin/Protein Technologies, Inc., Symphony peptide synthesizer. See, e.g., Antibodies: A Laboratory Manual, Chapter 5, pages 75-76, Harlow & Lane Eds., Cold Spring Harbor Laboratory (1988); Czernik, Methods In Enzymology (1991) 201:264-283; Merrifield, J. Am. Chem. Soc. (1962) 85:21-49.

This peptide was coupled to KLH, and rabbits were injected intradermally (ID) on the back with antigen in complete Freunds adjuvant (200 μg antigen per rabbit). The rabbits were boosted with same antigen in incomplete Freund adjuvant (100 μg antigen per rabbit) weekly for eight. Coincident with the dates of the third through eighth boosts, 15-20 mL bleed per rabbit was collected. One week after the eight boost, a terminating bleed of 40-60 mL per rabbit was collected. The sera were purified by Protein A-affinity chromatography as previously described (see Antibodies: A Laboratory Manual, Cold Spring Harbor, supra.). The eluted immunoglobulins were further loaded onto WHRRESDESGEC (SEQ ID NO: 23)-resin Knotes column. The flow through fraction was collected and applied onto WHRRES*DESGEC (SEQ ID NO: 22)-resin column. After washing the column extensively, the phospho-APG9L1-5735 antibodies were eluted and kept in antibody storage buffer.

The antibody was confirmed for phosphospecificity against the peptide antigen using Dot blot assay. 50 ng of phosphopeptide and 50 ng of the nonphosphorylated version of the peptide were spotted separately onto a nitrocellulose membrane. The membrane was allowed to dry. Non-specific sites were blocked by soaking in 5% BSA in TBS-T (0.5-1 hr, RT). A 10 cm petri dish was used for the reaction chamber. The membrane was incubated with the purified APG9L1-5735 phosphospecific polyclonal antibody at a concentration of 0.5 μg/mL dissolved in BSA/TBS-T for 30 min at room temperature. The membrane was washed three times with TBS-T (3×5 min). The membrane was incubated with secondary antibody conjugated to HRP using manufacturer's recommended dilution for 30 min at room temperature. The membrane was then washed three times with TBS-T (15 min×1, 5 min×2), then once with TBS (5 min). The membrane was then incubated with ECL reagent for 1 min, covered with Saran-wrap after removing excess solution from the surface, and then exposed to X-ray film in a dark room at several different lengths of exposure. The results of the dot blot is shown in FIG. 11. As shown in this Figure, the antibody, as expected, only recognized the phosphorylated peptide. It did not recognize the non-phosphorylated peptide.

Example 12 Production of an APG16L Serine-213 Phosphospecific Polyclonal Antibody

A 12 amino acid phospho-peptide antigen, CENEKDS*RRRQA (SEQ ID NO: 24) (where S*=phosphoserine), corresponding to residues 208-218 of human APG16L plus cysteine on the N-terminal for coupling, was constructed according to standard synthesis techniques using a Rainin/Protein Technologies, Inc., Symphony peptide synthesizer. See, e.g., Antibodies: A Laboratory Manual, Chapter 5, pages 75-76, Harlow & Lane Eds., Cold Spring Harbor Laboratory (1988); Czernik, Methods In Enzymology (1991) 201:264-283; Merrifield, J. Am. Chem. Soc. (1962) 85:21-49.

This peptide was coupled to KLH, and rabbits were injected intradermally (ID) on the back with antigen in complete Freunds adjuvant (200 μg antigen per rabbit). The rabbits were boosted with same antigen in incomplete Freund adjuvant (100 μg antigen per rabbit) weekly for eight. Coincident with the dates of the third through eighth boosts, 15-20 mL bleed per rabbit was collected. One week after the eight boost, a terminating bleed of 40-60 mL per rabbit was collected. The sera were purified by Protein A-affinity chromatography as previously described (see Antibodies: A Laboratory Manual, Cold Spring Harbor, supra.). The eluted immunoglobulins were further loaded onto CENEKDSRRRQA (SEQ ID NO: 25)-resin Knotes column. The flow through fraction was collected and applied onto CENEKDS*RRRQA (SEQ ID NO: 24)-resin column. After washing the column extensively, the phospho-APG16L-S213 antibodies were eluted and kept in antibody storage buffer.

The antibody was confirmed for phosphospecificity against the peptide antigen using Dot blot assay. 50 ng of phosphopeptide and 50 ng of the nonphosphorylated version of the peptide were spotted separately onto a nitrocellulose membrane. The membrane was allowed to dry. Non-specific sites were blocked by soaking in 5% BSA in TBS-T (0.5-1 hr, RT). A 10 cm petri dish was used for the reaction chamber. The membrane was incubated with the purified APG16L-S213 phosphospecific polyclonal antibody at a concentration of 0.5 μg/mL dissolved in BSA/TBS-T for 30 min at room temperature. The membrane was washed three times with TBS-T (3×5 min). The membrane was incubated with secondary antibody conjugated to HRP using manufacturer's recommended dilution for 30 min at room temperature. The membrane was then washed three times with TBS-T (15 min×1, 5 min×2), then once with TBS (5 min). The membrane was then incubated with ECL reagent for 1 min, covered with Saran-wrap after removing excess solution from the surface, and then exposed to X-ray film in a dark room at several different lengths of exposure. The results of the dot blot is shown in FIG. 12. As shown in this Figure, the antibody, as expected, only recognized the phosphorylated peptide. It did not recognize the non-phosphorylated peptide.

Example 13 Production of an APG16L Serine-287 Phosphospecific Polyclonal Antibody

A 12 amino acid phospho-peptide antigen, IFGRRS*VSSFPC (SEQ ID NO: 26) (where S*=phosphoserine), corresponding to residues 282-292 of human APG16L plus cysteine on the C-terminal for coupling, was constructed according to standard synthesis techniques using a Rainin/Protein Technologies, Inc., Symphony peptide synthesizer. See, e.g., Antibodies: A Laboratory Manual, Chapter 5, pages 75-76, Harlow & Lane Eds., Cold Spring Harbor Laboratory (1988); Czernik, Methods In Enzymology (1991) 201:264-283; Merrifield, J. Am. Chem. Soc. (1962) 85:21-49.

This peptide was coupled to KLH, and rabbits were injected intradermally (ID) on the back with antigen in complete Freunds adjuvant (200 μg antigen per rabbit). The rabbits were boosted with same antigen in incomplete Freund adjuvant (100 μg antigen per rabbit) weekly for eight. Coincident with the dates of the third through eighth boosts, 15-20 mL bleed per rabbit was collected. One week after the eight boost, a terminating bleed of 40-60 mL per rabbit was collected. The sera were purified by Protein A-affinity chromatography as previously described (see Antibodies: A Laboratory Manual, Cold Spring Harbor, supra.). The eluted immunoglobulins were further loaded onto IFGRRSVSSFPC (SEQ ID NO: 27)-resin Knotes column. The flow through fraction was collected and applied onto IFGRRS*VSSFPC (SEQ ID NO: 26)-resin column. After washing the column extensively, the phospho-APG16L-5287 antibodies were eluted and kept in antibody storage buffer.

The antibody was confirmed for phosphospecificity against the peptide antigen using Dot blot assay. 50 ng of phosphopeptide and 50 ng of the nonphosphorylated version of the peptide were spotted separately onto a nitrocellulose membrane. The membrane was allowed to dry. Non-specific sites were blocked by soaking in 5% BSA in TBS-T (0.5-1 hr, RT). A 10 cm petri dish was used for the reaction chamber. The membrane was incubated with the purified APG16L-5287 phosphospecific polyclonal antibody at a concentration of 0.5 μg/mL dissolved in BSA/TBS-T for 30 min at room temperature. The membrane was washed three times with TBS-T (3×5 min). The membrane was incubated with secondary antibody conjugated to HRP using manufacturer's recommended dilution for 30 min at room temperature. The membrane was then washed three times with TBS-T (15 min×1, 5 min×2), then once with TBS (5 min). The membrane was then incubated with ECL reagent for 1 min, covered with Saran-wrap after removing excess solution from the surface, and then exposed to X-ray film in a dark room at several different lengths of exposure. The results of the dot blot is shown in FIG. 13. As shown in this Figure, the antibody, as expected, only recognized the phosphorylated peptide. It did not recognize the non-phosphorylated peptide.

The following are further exemplary embodiments:

1. An isolated autophagy peptide comprising an amino acid sequence selected from the group consisting of sequences set forth in Table 1, wherein the x residue is nonphosphorylated or phosphorylated serine, threonine, or tyrosine, and with the proviso that the peptide is not a full-length autophagy protein.

2. An isolated autophagy peptide of embodiment 1 wherein the peptide does not comprise a sequence set forth in Table 2.

3. The isolated autophagy peptide of embodiment 1, which comprises an amino acid sequence selected from the group consisting of the sequences set forth in Table 3.

4. The isolated autophagy peptide of embodiment 1, which comprises an amino acid sequence selected from the group consisting of sequences set forth in Table 1.

5. The isolated autophagy peptide of embodiment 4, wherein the x residue is nonphosphorylated or phosphorylated serine, threonine, or tyrosine.

6. The isolated autophagy peptide of embodiment 1, wherein the x residue is phosphorylated serine, threonine, or tyrosine.

7. A pharmaceutical composition, which comprises an isolated autophagy peptide of embodiment 1 and a pharmaceutically acceptable carrier and excipient.

8. The isolated autophagy peptide of embodiment 1, which is conjugated to a carrier to enhance the peptide's immunogenicity.

9. The isolated autophagy peptide of embodiment 8, wherein the carrier is a carrier protein.

10. The isolated autophagy peptide of embodiment 9, wherein the autophagy peptide and the carrier protein are parts of a fusion protein.

11. An immunogen, which immunogen comprises:

(a) an isolated autophagy peptide of embodiment 1; and

(b) an immune response potentiator.

12. The immunogen of embodiment 11, wherein the immune response potentiator is selected from the group consisting of Bacille Calmette-Guerin (BCG), Corynebacterium Parvum, Brucella abortus extract, glucan, levamisole, tilorone, an enzyme and a non-virulent virus.

13. A multiple antigenic peptide (MAP), which MAP comprises a branched oligolysine core conjugated with a plurality of an isolated autophagy peptide of embodiment 1.

14. The MAP of embodiment 13, wherein the branched oligolysine core comprises 3, 7 or 15 lysine residues.

15. The MAP of embodiment 13, wherein the plurality of the autophagy peptide is conjugated to the branched oligolysine core via a spacer.

16. The MAP of embodiment 13, wherein the spacer is one or more amino acid residues.

17. The MAP of embodiment 13, which comprises 4, 8 or 16 copies of the autophagy peptide.

18. The MAP of embodiment 13, wherein the plurality of the autophagy peptide comprises same or different peptides.

19. A method for producing an antibody to an autophagy polypeptide, which method comprises:

(a) introducing an isolated autophagy peptide of embodiment 1 to a mammal in an amount sufficient to produce an antibody to said autophagy peptide; and

(b) recovering said antibody from said mammal.

20. The method of embodiment 19, wherein the x residue in the isolated autophagy peptide is nonphosphorylated serine, threonine, or tyrosine and the method is used to produce an antibody to a nonphosphorylated autophagy polypeptide.

21. The method of embodiment 19, wherein the x residue in the isolated autophagy peptide is phosphorylated serine, threonine, or tyrosine and the method is used to produce an antibody to a phosphorylated autophagy polypeptide.

22. The method of embodiment 21, which further comprises a step of removing an antibody that binds to an isolated autophagy peptide of embodiment 1 wherein x is nonphosphorylated serine, threonine, or tyrosine.

23. The method of embodiment 19, wherein the isolated autophagy peptide is conjugated to a carrier to enhance the peptide's immunogenicity.

24. The method of embodiment 19, wherein the isolated autophagy peptide is comprised in an immunogen of embodiment 10 or a MAP of embodiment 12.

25. An antibody to an autophagy polypeptide produced by the method of embodiment 19.

26. A kit for producing an antibody to an autophagy polypeptide, which kit comprises:

(a) an isolated autophagy peptide of embodiment 1;

(b) means for introducing said isolated autophagy peptide to a mammal in an amount sufficient to produce an antibody to said autophagy peptide; and

(c) means for recovering said antibody from said mammal.

27. A method for producing an antibody to an autophagy polypeptide, which method comprises:

(a) introducing an autophagy polypeptide to a mammal in an amount sufficient to produce an antibody to said autophagy polypeptide;

(b) recovering said antibody from said mammal; and

(c) affinity purifying an autophagy antibody that specifically binds to an epitope comprised in an autophagy peptide of embodiment 1 using said autophagy peptide.

28. The method of embodiment 27, wherein the autophagy polypeptide comprises a full-length autophagy protein.

29. The method of embodiments 27 and 28, wherein the x residue of the autophagy polypeptide is nonphosphorylated serine, threonine, or tyrosine and the method is used to produce an antibody to a nonphosphorylated autophagy polypeptide.

30. The method of embodiments 27 and 28, wherein the autophagy polypeptide is an autophagy polypeptide comprising a sequence set forth in Table 4, the x residue in any sequence set forth in Table 4 is phosphorylated serine, threonine, or tyrosine, and the method is used to produce an antibody to a phosphorylated autophagy polypeptide.

31. The method of embodiment 30, which further comprises a step of removing an antibody that binds to an isolated autophagy peptide of embodiment 1 wherein the x residue is nonphosphorylated serine, threonine, or tyrosine.

32. An antibody to an autophagy polypeptide produced by the method of embodiment 26.

33. A kit for producing an antibody to an autophagy polypeptide, which kit comprises:

(a) an autophagy protein;

(b) means for introducing said an autophagy protein to a mammal in an amount sufficient to produce an antibody to said autophagy polypeptide;

(c) means for recovering said antibody from said mammal; and

(d) an isolated autophagy peptide of embodiment 1.

34. An isolated antibody that specifically binds to an epitope that comprises the amino acid residue x in an amino acid sequence set forth in Table 4, wherein x is serine, threonine, tyrosine, phosphoserine, phosphothreonine or phosphotyrosine.

35. The isolated antibody of embodiment 34, wherein the epitope comprises the amino acid residue x in the amino acid sequence set forth in Table 4 and an amino acid residue of an autophagy protein that is outside the amino acid sequence set forth in Table 4.

36. The isolated antibody of embodiment 34, wherein the epitope comprises the amino acid residue x in an amino acid sequence set forth in Table 4 and amino acid residues of an autophagy protein that are outside the amino acid sequence set forth in Table 4.

37. The isolated antibody of embodiment 34, wherein the epitope is comprised in an amino acid sequence set forth in Table 4.

38. The isolated antibody of embodiment 34, wherein the epitope is comprised of an amino acid sequence set forth in Table 3.

39. The isolated antibody of embodiment 34, wherein the epitope is comprised of an amino acid sequence set forth in Table 1.

40. The isolated antibody of embodiment 34, which specifically binds to the epitope that comprises the x residue in the amino acid sequence set forth in Table 4, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine.

41. The isolated antibody of embodiment 34, which specifically binds to the epitope that comprises the x residue in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated serine, threonine, or tyrosine.

42. The isolated antibody of embodiment 34, which specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine, but does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated serine, threonine, or tyrosine.

43. The isolated antibody of embodiment 34, which specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated serine, threonine, or tyrosine, but does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine.

44. The isolated antibody of embodiment 43, wherein the amino acid sequence set forth in Table 4 is comprised in an autophagy protein or fragment.

45. The isolated antibody of embodiment 44, wherein the amino acid sequence set forth in Table 4 is comprised in a full length autophagy protein and the isolated antibody specifically binds to the full length autophagy protein.

46. The isolated antibody of embodiment 45, which specifically binds to the full length autophagy protein when the x residue is nonphosphorylated serine, threonine, or tyrosine in the amino acid sequence set forth in Table 4 but does not specifically bind to the full length autophagy protein when the x residue is phosphorylated serine, threonine, or tyrosine in the amino acid sequence set forth in Table 4.

47. The isolated antibody of embodiment 45, which specifically binds to the full length autophagy protein when the x residue is phosphorylated serine, threonine, or tyrosine in the amino acid sequence set forth in Table 4 but does not specifically bind to the full length autophagy protein when the x residue is nonphosphorylated serine, threonine, or tyrosine in the amino acid sequence set forth in Table 4.

48. The isolated antibody of embodiment 45, which specifically binds to the full length autophagy protein at its natural conformation.

49. The isolated antibody of embodiment 34, which is a monoclonal or polyclonal antibody or an antibody fragment.

50. A method for detecting an autophagy protein or fragment comprising an amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated or nonphosphorylated serine, threonine, or tyrosine in a sample, which method comprises:

(a) contacting a sample containing or suspected of containing an autophagy protein or fragment comprising the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated or nonphosphorylated serine, threonine, or tyrosine, with an isolated antibody that specifically binds to an epitope that comprises the amino acid residue x in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated or nonphosphorylated serine, threonine, or tyrosine; and

(b) assessing a complex formed between said autophagy protein or fragment, if present in said sample, and said antibody, to determine the presence, absence and/or amount of said autophagy protein or fragment in said sample.

51. The method of embodiment 50, wherein the epitope comprises the amino acid residue x in the amino acid sequence set forth in Table 4 and an amino acid residue of the autophagy protein that is outside the amino acid sequence set forth in Table 4.

52. The method of embodiment 50, wherein the epitope comprises the amino acid residue x in the amino acid sequence set forth in Table 4 and amino acid residues of the autophagy protein that are outside the amino acid sequence set forth in Table 4.

53. The method of embodiment 50, wherein the epitope is comprised in the amino acid sequence set forth in Table 4.

54. The method of embodiment 50, wherein the epitope is comprised in an amino acid sequence set forth in Table 3.

55. The method of embodiment 50, wherein the epitope is comprised in an amino acid sequence selected from the sequence set forth in Table 1.

56. The method of embodiment 50, wherein the isolated antibody specifically binds to the epitope that comprises the x residue in the amino acid sequence set forth in Table 4, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine.

57. The method of embodiment 50, wherein the isolated antibody specifically binds to the epitope that comprises the x residue in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated serine, threonine, or tyrosine.

58. The method of embodiment 50, wherein the isolated antibody specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine, but does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated serine, threonine, or tyrosine.

59. The method of embodiment 50, wherein the isolated antibody specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated serine, threonine, or tyrosine, but does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine.

60. The method of embodiment 50, wherein the amino acid sequence set forth in Table 4 is comprised in a full length autophagy protein and the isolated antibody specifically binds to the full length autophagy protein.

61. The method of embodiment 60, wherein the isolated antibody specifically binds to the full length autophagy protein when the x residue is nonphosphorylated serine, threonine, or tyrosine in the amino acid sequence set forth in Table 4 but does not specifically bind to the full length autophagy protein when the x residue is phosphorylated serine, threonine, or tyrosine in the amino acid sequence set forth in Table 4 to determine the presence, absence and/or amount of nonphosphorylated full length autophagy protein in the sample.

62. The method of embodiment 60, wherein the isolated antibody specifically binds to the full length autophagy protein when the x residue is phosphorylated serine, threonine, or tyrosine in the amino acid sequence set forth in Table 4 but does not specifically bind to the full length autophagy protein when the x residue is nonphosphorylated serine, threonine, or tyrosine in the amino acid sequence set forth in Table 4 to determine the presence, absence and/or amount of phosphorylated full length autophagy protein in the sample.

63. The method of embodiment 50, wherein the isolated antibody specifically binds to the full length autophagy protein at its natural conformation.

64. The method of embodiment 50, wherein the isolated antibody is a monoclonal or polyclonal antibody or antibody fragment.

65. The method of embodiment 50, wherein the complex is assessed by a sandwich or competitive assay format.

66. The method of embodiment 65, wherein the antibody that that specifically binds to an epitope that comprises the amino acid residue x in the amino acid sequence set forth in Table 4 is used as a first antibody and an antibody that is capable of binding to a portion of an autophagy protein or fragment other than the portion that binds to the first antibody is used as a second antibody in a sandwich assay format.

67. The method of embodiment 66, wherein either the first antibody or the second antibody is attached to a surface and functions as a capture antibody.

68. The method of embodiment 67, wherein the capture antibody is attached to the surface directly or indirectly.

69. The method of embodiment 67, wherein the capture antibody is attached to the surface via a biotin-avidin (or streptavidin) linking pair.

70. The method of embodiment 50, wherein the complex is assessed by a format selected from the group consisting of an enzyme-linked immunosorbent assay (ELISA), immunoblotting, immunoprecipitation, radioimmunoassay (RIA), immunostaining, latex agglutination, indirect hemagglutination assay (IHA), complement fixation, indirect immunofluorescent assay (IFA), nephelometry, flow cytometry assay, plasmon resonance assay, chemiluminescence assay, lateral flow immunoassay, u-capture assay, inhibition assay and avidity assay.

71. The method of embodiment 50, wherein the complex is assessed in a homogeneous or a heterogeneous assay format.

72. The method of embodiment 50, which is used to determine the phosphorylation status of an autophagy protein or fragment comprising the amino acid sequence set forth in Table 4.

73. The method of embodiment 72, which is used to determine the phosphorylation status of a full length autophagy protein.

74. The method of embodiment 73, which is used to determine the phosphorylation status of a full length autophagy protein in a biological sample.

75. The method of embodiment 74, wherein the biological sample is a clinical sample.

76. The method of embodiment 74, which is used for the prognosis, diagnosis and/or treatment monitoring of a disease or disorder associated with abnormal phosphorylation status of an autophagy polypeptide comprising the amino acid sequence set forth in Table 4.

77. The method of embodiment 76, wherein the autophagy protein is a full length autophagy protein.

78. The method of embodiment 76, wherein the disease or disorder associated with abnormal phosphorylation status of an autophagy protein or fragment is selected from the group consisting of ischemic brain injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, prion diseases and polyglutamine disorders including Huntington's disease and various spinocerebellar ataxias, transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease, breast cancer, ovarian cancer, brain cancer, pancreatic cancer, esophageal cancer, colorectal cancer, liver cancer, prostate cancer, renal cancer, lung cancer, Myocardial ischemia, cardiac remodeling, cardiomyopathy, hemodynamic stress, myocardial hypertrophy, Neuronal ceroid-lipofuscinosis (adult and juvenile), Multiple Sulfatase Deficiency (MSD) and Mucopolysaccharidosis type IIIA, Batten disease, Niemann-Pick C, Danon disease, Pompe disease, and dysfunction of innate and adaptive immunity against intracellular pathogens.

79. A kit for detecting an autophagy protein or fragment comprising amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated or nonphosphorylated serine, threonine, or tyrosine, in a sample, which kit comprises, in a container, an isolated antibody that specifically binds to an epitope that comprises the x residue in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated or nonphosphorylated serine, threonine, or tyrosine.

80. A method for treating a disease or disorder associated with abnormal phosphorylation status of an autophagy protein or fragment comprising amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated or nonphosphorylated serine, threonine, or tyrosine, which method comprises administering, to a subject when such a treatment is needed or desired, a sufficient amount of an isolated antibody that specifically binds to an epitope that comprises the amino acid residue x in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated or nonphosphorylated serine, threonine, or tyrosine.

81. The method of embodiment 80, wherein the isolated antibody specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein x residue is nonphosphorylated serine, threonine, or tyrosine, but does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated serine, threonine, or tyrosine.

82. The method of embodiment 81, wherein the disease or disorder is associated with abnormally high phosphorylation level of an autophagy protein or fragment, and the binding of the antibody to the autophagy protein or fragment prevents or reduces phosphorylation level of the autophagy protein or fragment.

84. The method of embodiment 80, wherein the isolated antibody specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated serine, threonine, or tyrosine, but does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine.

85. The method of embodiment 84, wherein the disease or disorder is associated with abnormally low phosphorylation level of an autophagy protein or fragment, and the binding of the antibody to the autophagy protein or fragment prevents or reduces dephosphorylation of the autophagy protein or fragment.

86. The method of embodiments 82 and 85, wherein the disease or disorder associated with abnormally low phosphorylation level of an autophagy protein is selected from the group consisting of ischemic brain injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, prion diseases and polyglutamine disorders including Huntington's disease and various spinocerebellar ataxias, transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease, breast cancer, ovarian cancer, brain cancer, pancreatic cancer, esophageal cancer, colorectal cancer, liver cancer, prostate cancer, renal cancer, lung cancer, Myocardial ischemia, cardiac remodeling, cardiomyopathy, hemodynamic stress, myocardial hypertrophy, Neuronal ceroid-lipofuscinosis (adult and juvenile), Multiple Sulfatase Deficiency (MSD) and Mucopolysaccharidosis type IIIA, Batten disease, Niemann-Pick C, Danon disease, Pompe disease, and dysfunction of innate and adaptive immunity against intracellular pathogens

87. The method of embodiment 80, wherein the amino acid sequence set forth in Table 4 is comprised in a full length autophagy protein and the isolated antibody specifically binds to the full length autophagy protein.

88. The method of embodiment 87, wherein the isolated antibody specifically binds to the full length autophagy protein when the x residue is nonphosphorylated serine, threonine, or tyrosine in the amino acid sequence set forth in Table 4 but does not specifically bind to the full length autophagy protein when the x residue is phosphorylated serine, threonine, or tyrosine in the amino acid sequence set forth in Table 4.

89. The method of embodiment 87, wherein the isolated antibody specifically binds to the full length autophagy protein when the x is phosphorylated serine, threonine, or tyrosine in the amino acid sequence set forth in Table 4 but does not specifically bind to the full length autophagy protein when the x residue is nonphosphorylated serine, threonine, or tyrosine in the amino acid sequence set forth in Table 4.

90. The method of embodiment 80, wherein the isolated antibody specifically binds to the full length autophagy protein at its natural conformation.

91. The method of embodiment 80, wherein the isolated antibody is a monoclonal or polyclonal antibody or antibody fragment.

92. The method of embodiment 80, which further comprises administering a pharmaceutically acceptable carrier and excipient.

93. The method of embodiment 80, wherein the subject is a mammal.

94. The method of embodiment 93, wherein the mammal is a human.

95. A pharmaceutical composition, which comprises an isolated antibody of embodiment 80 and a pharmaceutically acceptable carrier and excipient.

96. A method for identifying a kinase that phosphorylates an autophagy protein on the nonphosphorylated serine, threonine, or tyrosine at the x residue , which method comprises:

(a) providing an autophagy polypeptide comprising an amino acid sequence selected from a sequence set forth in Table 1, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine;

(b) contacting said autophagy polypeptide with a test protein and ATP under conditions suitable for the phosphorylation of said x residue of said autophagy polypeptide; and

(c) assessing phosphorylation status of said autophagy polypeptide to determine whether said test protein is a kinase for said autophagy protein on the nonphosphorylated serine, threonine, or tyrosine at the x residue.

97. The method of embodiment 96, wherein the autophagy protein or fragment comprises an amino acid sequence set forth in Table 4 wherein the x residue is nonphosphorylated serine, threonine, or tyrosine.

98. The method of embodiment 96, wherein the phosphorylation status of the autophagy polypeptide is assessed by an isolated antibody that specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated serine, threonine, or tyrosine, but does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine.

99. A method for identifying a modulator of a kinase that phosphorylates an autophagy protein on the x residue, which method comprises:

(a) providing an autophagy polypeptide comprising an amino acid sequence in set forth in Table 1, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine;

(b) contacting said autophagy polypeptide with a kinase that phosphorylates an autophagy protein on the nonphosphorylated x residue of serine, threonine, or tyrosine and ATP under conditions suitable for the phosphorylation of said x residue of said autophagy polypeptide in the presence or absence of a test substance; and

(c) assessing and comparing phosphorylation status of said autophagy polypeptide by said kinase to determine whether said test substance modulates said kinase.

100. The method of embodiment 99, wherein the autophagy protein or fragment comprises an amino acid sequence set forth in Table 4 wherein the x residue is nonphosphorylated serine, threonine, or tyrosine.

101. The method of embodiment 99, wherein the phosphorylation status of the autophagy polypeptide is assessed by an isolated antibody that specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein x is phosphoserine, but does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine.

102. A method for identifying a phosphatase that dephosphorylates an autophagy protein on the phosphorylated x residue of serine, threonine, or tyrosine, which method comprises:

(a) providing an autophagy polypeptide comprising an amino acid sequence set forth in Table 1, wherein the x residue is phosphorylated serine, threonine, or tyrosine;

(b) contacting said autophagy polypeptide with a test protein and H₂O under conditions suitable for the dephosphorylation of said x residue of said autophagy polypeptide; and

(c) assessing phosphorylation status of said autophagy polypeptide to determine whether said test protein is a phosphatase for said autophagy protein on the phosphorylated x residue of serine, threonine, or tyrosine.

103. The method of embodiment 102, wherein the autophagy protein or fragment comprises an amino acid sequence set forth in Table 4 wherein the x residue is phosphorylated serine, threonine, or tyrosine.

104. The method of embodiment 103, wherein the phosphorylation status of the autophagy polypeptide is assessed by an isolated antibody that specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine, but does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated serine, threonine, or tyrosine.

105. A method for identifying a modulator of a phosphatase that dephosphorylates an autophagy protein on the phosphorylated x residue of serine, threonine, or tyrosine, which method comprises:

(a) providing said autophagy polypeptide comprising an amino acid sequence in set forth in Table 1, wherein the x residue is phosphorylated serine, threonine, or tyrosine;

(b) contacting said autophagy polypeptide with a phosphatase that dephosphorylates an autophagy protein on the phosphorylated x residue of serine, threonine, or tyrosine and H₂O under conditions suitable for the dephosphorylation of said phosphoserine residue of said autophagy polypeptide in the presence or absence of a test substance; and

(c) assessing and comparing dephosphorylation status of said autophagy polypeptide by said phosphatase to determine whether said test substance modulates said phosphatase.

106. The method of embodiment 105, wherein the autophagy protein or fragment comprises an amino acid sequence set forth in Table 4 wherein the x residue is phosphorylated serine, threonine, or tyrosine.

107. The method of embodiment 106, wherein the phosphorylation status of the autophagy polypeptide is assessed by an isolated antibody that specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein x is nonphosphorylated serine, threonine, or tyrosine, but does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated serine, threonine, or tyrosine.

108. An isolated nucleic acid fragment, which isolated nucleic acid fragment comprises a sequence of nucleotides encoding an autophagy peptide comprising an amino acid sequence set forth in Table 1, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine, and with the proviso that the peptide is not a full-length autophagy protein comprising an amino acid sequence set forth in Table 2.

109. The isolated nucleic acid fragment of embodiment 108, wherein the autophagy peptide comprises an amino acid sequence set forth in Table 4.

110. The isolated nucleic acid fragment of embodiment 108, wherein the nucleic acid is DNA.

111. The isolated nucleic acid fragment of embodiment 108, wherein the nucleic acid is RNA.

112. A plasmid, which plasmid comprises the nucleic acid fragment of embodiment 108.

113. A vector, which vector comprises the nucleic acid fragment of embodiment 108.

114. A cell, which cell comprises the plasmid of embodiment 112 or the vector of embodiment 113.

115. The cell of embodiment 114, which is selected from the group consisting of a bacterial cell, a yeast cell, a fungal cell, a plant cell, an insect cell, an animal cell and a human cell.

116. A method for producing an autophagy peptide, which method comprises growing the cell of embodiment 114 under conditions whereby said autophagy peptide is expressed by the cell, and recovering said expressed autophagy peptide.

117. The method of embodiment 116, further comprises a step of phosphorylating the autophagy peptide at the nonphosphorylated x residue of serine, threonine, or tyrosine.

118. A method for identifying a compound that binds specifically to a phosphorylated autophagy polypeptide, which method comprises:

a) providing a phosphorylated autophagy polypeptide comprising an amino acid sequence set forth in Table 1, wherein the x residue is phosphorylated serine, threonine, or tyrosine;

b) contacting said phosphorylated autophagy polypeptide with a test compound under conditions suitable for binding of the test protein with the autophagy polypeptide;

c) assessing binding of the phosphorylated autophagy polypeptide with the test compound;

d) providing a nonphosphorylated autophagy polypeptide comprising an amino acid sequence selected set forth in Table 1, wherein the x residue is phosphorylated serine, threonine, or tyrosine;

e) contacting said nonphosphorylated autophagy polypeptide with the test compound under conditions suitable for binding of the test protein with the autophagy polypeptide;

f) assessing binding of the nonphosphorylated autophagy polypeptide with the test compound

wherein the compound that binds specifically to a phosphorylated autophagy polypeptide is a test compound which binds to phosphorylated autophagy polypeptide according to step c) but does not bind to nonphosphorylated autophagy polypeptide according to step e).

119. A method for identifying a compound that binds to specifically to a nonphosphorylated autophagy polypeptide, which method comprises:

a) providing a nonphosphorylated autophagy polypeptide comprising an amino acid sequence set forth in Table 1, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine;

b) contacting said nonphosphorylated autophagy polypeptide with a test compound under conditions suitable for binding of the test protein with autophagy polypeptide;

c) assessing binding of the nonphosphorylated autophagy polypeptide with the test compound;

d) providing a phosphorylated autophagy polypeptide comprising an amino acid sequence set forth in Table 1, wherein the x residue is phosphorylated serine, threonine, or tyrosine;

e) contacting said phosphorylated autophagy polypeptide with the test compound and under conditions suitable for binding of the test protein with autophagy polypeptide;

f) assessing binding of the phosphorylated autophagy polypeptide with the test compound

wherein the compound that binds specifically to a nonphosphorylated autophagy polypeptide is a test compound which binds to nonphosphorylated autophagy polypeptide according to step c) but does not bind to phosphorylated autophagy polypeptide according to step e).

120. The methods of embodiments 118 and 119, wherein the test compound is a protein.

121. The methods of embodiments 118 and 119, wherein the test compound is a peptide.

122. The methods of embodiments 118 and 119, wherein the test compound is a nucleic acid.

123. The methods of embodiments 118 and 119, wherein the test compound is a small molecule.

124. A method of treating a disease comprising modulating phosphorylation status of an autophagy polypeptide by administering an autophagy antibody, an autophagy peptide, or compounds from the screening process of embodiments 107 and 118-123, wherein the disease is selected from the group consisting of ischemic brain injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, prion diseases and polyglutamine disorders including Huntington's disease and various spinocerebellar ataxias, transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease, breast cancer, ovarian cancer, brain cancer, pancreatic cancer, esophageal cancer, colorectal cancer, liver cancer, prostate cancer, renal cancer, lung cancer, Myocardial ischemia, cardiac remodeling, cardiomyopathy, hemodynamic stress, myocardial hypertrophy, Neuronal ceroid-lipofuscinosis (adult and juvenile), Multiple Sulfatase Deficiency (MSD) and Mucopolysaccharidosis type IIIA, Batten disease, Niemann-Pick C, Danon disease, Pompe disease, and dysfunction of innate and adaptive immunity against intracellular pathogens.

125. A array comprising an antibody of embodiments 25, 32, and 34-49.

126. A method of array detection comprising use of an antibody of embodiments 25, 32, and 34-39.

127. A microarray comprising a solid support and a plurality of antibodies of embodiments 25, 32, and 34-49 immobilized on the solid support at a known predetermined position.

128. A microarray comprising a solid support and a plurality of polypeptides of embodiments 1-10.

129. The use of a microarray of embodiments 127-128 for assessing the phosphorylation status of a plurality of autophagy polypeptides in the autophagy pathway.

130. A method of monitoring the phosphorylation of an autophagy polypeptide, wherein the monitoring uses a microarray of embodiments 127-128.

131. A method of treating a disease comprising modulating the phosphorylation of an autophagy polypeptide at the x residue set forth in Table 4.

132. The method of embodiment 131, wherein the disease is selected from the group consisting of ischemic brain injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, prion diseases and polyglutamine disorders including Huntington's disease and various spinocerebellar ataxias, transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease, breast cancer, ovarian cancer, brain cancer, pancreatic cancer, esophageal cancer, colorectal cancer, liver cancer, prostate cancer, renal cancer, lung cancer, Myocardial ischemia, cardiac remodeling, cardiomyopathy, hemodynamic stress, myocardial hypertrophy, Neuronal ceroid-lipofuscinosis (adult and juvenile), Multiple Sulfatase Deficiency (MSD) and Mucopolysaccharidosis type IIIA, Batten disease, Niemann-Pick C, Danon disease, Pompe disease, and dysfunction of innate and adaptive immunity against intracellular pathogens.

133. The method of embodiments 131 and 132, wherein phosphorylation of the autophagy polypeptide is increased.

134. The method of embodiments 131 and 132, wherein phosphorylation of the autophagy polypeptide is decreased.

135. The method of embodiments 131, 133, and 134, wherein the phosphorylation status of the autophagy polypeptide is abnormal.

136. The method of embodiments 131, 133, and 134, wherein the phosphorylation status of the autophagy polypeptide is normal and wherein the disease is treatable by modulating the phosphorylation status of the autophagy polypeptide.

TABLE 1 Epitopes that include the phosphorylation site in autophagy proteins. Protein Name and NO Phosphorylation Site X equals: Sequence (SEQ ID NO) 1 APG3L-pY18 Tyrosine or Phosphotyrosine VAEX (28), AEXL (29), EXLT (30), XLTP (31) 2 APG3L-pY160 Tyrosine or Phosphotyrosine MEEX (32), EEXE (33), EXEE (34), XEES (35) 3 APG4A-pS6 Serine or Phosphoserine SVLX (36), VLXK (37), LXKY (38), XKYE (39) 4 APG4A-pS62 Serine or Phosphoserine RKFX (40), KFXP (41), FXPI (42), XPIG (43) 5 APG4A-pS100 Serine or Phosphoserine RDWX (44), DWXW (45), WXWE (46), XWEK (47) 6 APG4B-pS121 Serine or Phosphoserine RKDX (48), KDXY (49), DXYY (50), XYYS (51) 7 APG4B-pS309 Serine or Phosphoserine CRMX (52), RMXI (53), MXIA (54), XIAE (55) 8 APG4C-pS166 Serine or Phosphoserine ASLX (56), SLXG (57), LXGE (58), XGER (59) 9 APG4C-pS177 Serine or Phosphoserine PTIX (60), TIXL (61), IXLK (62), XLKE (63) 10 APG4C-pS224 Serine or Phosphoserine GKKX (64), KKXG (65), KXGK (66), XGKK (67) 11 APG4C-pS398 Serine or Phosphoserine KRAX (68), RAXE (69), AXEE (70), XEEI (71) 12 APG4C-S408 Serine or Phosphoserine LKFX (72), KFXS (73), FXSK (74), XSKE (75) 13 APG4C-pS451 Serine or Phosphoserine KRFX (76), RFXT (77), FXTE (78), XTEE (79) 14 APG4D-S15 Serine or Phosphoserine RSSX (80), SSXP (81), SXPE (82), XPED (83) 15 APG4D-pS341 Serine or Phosphoserine PRHX (84), RHXL (85), HXLY (86), XLYF (87) 16 APG4D-pS467 Serine or Phosphoserine KRPX (88), RPXS (89), PXSE (90), XSED (91) 17 APG5L-pY35 Tyrosine or Phosphotyrosine AEPX (92), EPXY (93), PXYL (94), XYLL (95) 18 APG5L-pS225 Serine or Phosphoserine VCPX (96), CPXA (97), PXAI (98), XAID (99) 19 APG7L-pS95 Serine or Phosphoserine TLEX (100), LEXF (101), EXFK (102), XFKT (103) 20 APG7L-pS173 Serine or Phosphoserine QRFX (104), RFXL (105), FXLK (106), XLKQ (107) 22 APG8b-pT12 Threonine or QRRX (108), RRXF (109), RXFE Phosphothreonine (110), XFEQ (111) 23 APG8b-pS101 Serine or Phosphoserine VYEX (112), YEXE (113), EXEK (114), XEKD (115) 25 APG8c-pS137 Serine or Phosphoserine RDGX (116), DGXS (117), GXSL (118), XSLE (119) 26 APG8c-pS137/138 Serine or Phosphoserine RDGXX (120), DGXXL (121), GXXLE (122), XXLED (123) 27 APG8c-pS138 Serine or Phosphoserine DGSX (124), GSXL (125), SXLE (126), XLED (127) 28 APG9L1-pS14 Serine or Phosphoserine LEAX (128), EAXY (129), AXYS (130), XYSD (131) 29 APG9L1-pY209 Tyrosine or Phosphotyrosine LDIX (132), DIXH (133), IXHR (134), XHRI (135) 30 APG9L1-pS613 Serine or Phosphoserine SLQX (136), LQXE (137), QXES (138), XESE (139) 31 APG9L1-pS735 Serine or Phosphoserine RREX (140), REXD (141), EXDE (142), XDES (143) 32 APG9L1-pS738 Serine or Phosphoserine SDEX (144), DEXG (145), EXGE (146), XGES (147) 33 APG9L1-pS741 Serine or Phosphoserine SGEX (148), GEXA (149), EXAP (150), XAPD (151) 34 APG9L1-pS828 Serine or Phosphoserine EEGX (152), EGXE (153), GXED (154), XEDE (155) 35 APG10L-pS116 Serine or Phosphoserine FRAX (156), RAXF (157), AXFL (158), XFLD (159) 36 APG12L-pS26 Serine or Phosphoserine TDVX (160), DVXP (161), VXPE (162), XPET (163) 37 APG12L-pS41 Serine or Phosphoserine AAVX (164), AVXP (165), VXPG (166), XPGT (167) 38 APG16L-pS213 Serine or Phosphoserine EKDX (168), KDXR (169), DXRR (170), XRRR (171) 39 APG16L-pS287 Serine or Phosphoserine GRRX (172), RRXV (173), RXVS (174), XVSS (175) 40 APG16L-pS304 Serine or Phosphoserine HPGX (176), PGXG (177), GXGK (178), XGKE (179) 41 BECN1-pS64 Serine or Phosphoserine ETNX (180), TNXG (181), NXGE (182), XGEE (183) 42 BECN1-pT72 Threonine or FIEX (184), IEXP (185), EXPR (186), Phosphothreonine XPRQ (187) 43 BECN1-pS249 Serine or Phosphoserine ELKX (188), LKXV (189), KXVE (190), XVEN (191)

TABLE 2 Full-length sequences of autophagy proteins. PRODUCT NCBI SEQ NO NAME Accession Sequence ID NO 1 APG3L NP_071933 MQNVINTVKGKALEVAEYLTPVLKESK 192 Y18, Y160 FKETGVITPEEFVAAGDHLVHHCPTWQ WATGEELKVKAYLPTGKQFLVTKNVP CYKRCKQMEYSDELEAIIEEDDGDGGW VDTYHNTGITGITEAVKEITLENKDNIR LQDCSALCEEEEDEDEGEAADMEEYEE SGLLETDEATLDTRKIVEACKAKTDAG GEDAILQTRTYDLYITYDKYYQTPRLW LFGYDEQRQPLTVEHMYEDISQDHVKK TVTIENHPHLPPPPMCSVHPCRHAEVM KKIIETVAEGGGELGVHMYLLIFLKFVQ AVIPTIEYDYTRHFTM 2 APG4A NP_443168 MESVLSKYEDQITIFTDYLEEYPDTDEL 193 S6, S62, VWILGKQHLLKTEKSKLLSDISARLWFT S100 YRRKFSPIGGTGPSSDAGWGCMLRCGQ MMLAQALICRHLGRDWSWEKQKEQPK EYQRILQCFLDRKDCCYSIHQMAQMGV GEGKSIGEWFGPNTVAQVLKKLALFDE WNSLAVYVSMDNTVVIEDIKKMCRVL PLSADTAGDRPPDSLTASNQSKGTSAY CSAWKPLLLIVPLRLGINQINPVYVDAF KECFKMPQSLGALGGKPNNAYYFIGFL GDELIFLDPHTTQTFVDTEENGTVNDQT FHCLQSPQRMNILNLDPSVALGFFCKEE KDFDNWCSLVQKEILKENLRMFELVQK HPSHWPPFVPPAKPEVTTTGAEFIDSTE QLEEFDLEEDFEILSV 3 APG4B NP_037457 MDAATLTYDTLRFAEFEDFPETSEPVWI 194 S121, S309 LGRKYSIFTEKDEILSDVASRLWFTYRK NFPAIGGTGPTSDTGWGCMLRCGQMIF AQALVCRHLGRDWRWTQRKRQPDSYF SVLNAFIDRKDSYYSIHQIAQMGVGEG KSIGQWYGPNTVAQVLKKLAVFDTWS SLAVHIAMDNTVVMEEIRRLCRTSVPC AGATAFPADSDRHCNGFPAGAEVTNRP SPWRPLVLLIPLRLGLTDINEAYVETLK HCFMMPQSLGVIGGKPNSAHYFIGYVG EELIYLDPHTTQPAVEPTDGCFIPDESFH CQHPPCRMSIAELDPSIAVGFFCKTEDD FNDWCQQVKKLSLLGGALPMFELVEL QPSHLACPDVLNLSLDSSDVERLERFFD SEDEDFEILSL 4 APG4C NP_835739 MEATGTDEVDKLKTKFISAWNNMKYS 195 S166, S177, WVLKTKTYFSRNSPVLLLGKCYHFKYE S224, S398, DEDKTLPAESGCTIEDHVIAGNVEEFRK S408, S451, DFISRIWLTYREEFPQIEGSALTTDCGW GCTLRTGQMLLAQGLILHFLGRAWTW PDALNIENSDSESWTSHTVKKFTASFEA SLSGEREFKTPTISLKETIGKYSDDHEM RNEVYHRKIISWFGDSPLALFGLHQLIE YGKKSGKKAGDWYGPAVVAHILRKAV EEARHPDLQGITIYVAQDCTVYNSDVID KQSASMTSDNADDKAVIILVPVRLGGE RTNTDYLEFVKGILSLEYCVGIIGGKPK QSYYFAGFQDDSLIYMDPHYCQSFVDV SIKDFPLETFHCPSPKKMSFRKMDPSCTI GFYCRNVQDFKRASEEITKMLKFSSKE KYPLFTFVNGHSRDYDFTSTTTNEEDLF SEDEKKQLKRFSTEEFVLL 5 APG4D NP_116274 MNSVSPAAAQYRSSSPEDARRRPEARR 196 S15, S341, PRGPRGPDPNGLGPSGASGPALGSPGA S467 GPSEPDEVDKFKAKFLTAWNNVKYGW VVKSRTSFSKISSIHLCGRRYRFEGEGDI QRFQRDFVSRLWLTYRRDFPPLPGGCL TSDCGWGCMLRSGQMMLAQGLLLHFL PRDWTWAEGMGLGPPELSGSASPSRYH GPARWMPPRWAQGAPELEQERRHRQI VSWFADHPRAPFGLHRLVELGQSSGKK AGDWYGPSLVAHILRKAVESCSDVTRL VVYVSQDCTVYKADVARLVARPDPTA EWKSVVILVPVRLGGETLNPVYVPCVK ELLRCELCLGIMGGKPRHSLYFIGYQDD FLLYLDPHYCQPTVDVSQADFPLESFHC TSPRKMAFAKMDPSCTVGFYAGDRKE FETLCSELTRVLSSSSATERYPMFTLAE GHAQDHSLDDLCSQLAQPTLRLPRTGR LLRAKRPSSEDFVFL 6 APG5L NP_004840 MTDDKDVLRDVWFGRIPTCFTLYQDEI 197 Y35, S225 TEREAEPYYLLLPRVSYLTLVTDKVKK HFQKVMRQEDISEIWFEYEGTPLKWHY PIGLLFDLLASSSALPWNITVHFKSFPEK DLLHCPSKDAIEAHFMSCMKEADALKH KSQVINEMQKKDHKQLWMGLQNDRF DQFWAINRKLMEYPAEENGFRYIPFRIY QTTTERPFIQKLFRPVAADGQLHTLGDL LKEVCPSAIDPEDGEKKNQVMIHGIEPM LETPLQWLSEHLSYPDNFLHISIIPQPTD 7 APG7L NP_006386 MAAATGDPGLSKLQFAPFSSALDVGFW 198 S95, S173 HELTQKKLNEYRLDEAPKDIKGYYYNG DSAGLPARLTLEFSAFDMSAPTPARCCP AIGTLYNTNTLESFKTADKKLLLEQAA NEIWESIKSGTALENPVLLNKFLLLTFA DLKKYHFYYWFCYPALCLPESLPLIQGP VGLDQRFSLKQIEALECAYDNLCQTEG VTALPYFLIKYDENMVLVSLLKHYSDF FQGQRTKITIGVYDPCNLAQYPGWPLR NFLVLAAHRWSSSFQSVEVVCFRDRTM QGARDVAHSIIFEVKLPEMAFSPDCPKA VGWEKNQKGGMGPRMVNLSECMDPK RLAESSVDLNLKLMCWRLVPTLDLDK VVSVKCLLLGAGTLGCNVARTLMGWG VRHITFVDNAKISYSNPVRQPLYEFEDC LGGGKPKALAAADRLQKIFPGVNARGF NMSIPMPGHPVNFSSVTLEQARRDVEQ LEQLIESHDVVFLLMDTRESRWLPAVIA ASKRKLVINAALGFDTFVVMRHGLKKP KQQGAGDLCPNHPVASADLLGSSLFAN IPGYKLGCYFCNDVVAPGDSTRDRTLD QQCTVSRPGLAVIAGALAVELMVSVLQ HPEGGYAIASSSDDRMNEPPTSLGLVPH QIRGFLSRFDNVLPVSLAFDKCTACSSK VLDQYEREGFNFLAKVFNSSHSFLEDLT GLTLLHQETQAAEIWDMSDDETI 9 APG8b NP_073729 MPSEKTFKQRRTFEQRVEDVRLIREQHP 199 T12, S101 TKIPVIIERYKGEKQLPVLDKTKFLVPD HVNMSELIKIIRRRLQLNANQAFFLLVN GHSMVSVSTPISEVYESEKDEDGFLYM VYASQETFGMKLSV 10  APG8c NP_073729 MPSEKTFKQRRTFEQRVEDVRLIREQHP 200 S137, TKIPVIIERYKGEKQLPVLDKTKFLVPD S137/S138, HVNMSELIKIIRRRLQLNANQAFFLLVN S138 GHSMVSVSTPISEVYESEKDEDGFLYM VYASQETFGMKLSV 11  APG9L1 NP_076990 MAQFDTEYQRLEASYSDSPPGEEDLLV 201 S14, Y209, HVAEGSKSPWHHIENLDLFFSRVYNLH S613, S735, QKNGFTCMLIGEIFELMQFLFVVAFTTF S738, S741, LVSCVDYDILFANKMVNHSLHPTEPVK S828 VTLPDAFLPAQVCSARIQENGSLITILVI AGVFWIHRLIKFIYNICCYWEIHSFYLH ALRIPMSALPYCTWQEVQARIVQTQKE HQICIHKRELTELDIYHRILRFQNYMVA LVNKSLLPLRFRLPGLGEAVFFTRGLKY NFELILFWGPGSLFLNEWSLKAEYKRG GQRLELAQRLSNRILWIGIANFLLCPLIL IWQILYAFFSYAEVLKREPGALGARCW SLYGRCYLRHFNELEHELQSRLNRGYK PASKYMNCFLSPLLTLLAKNGAFFAGSI LAVLIALTIYDEDVLAVEHVLTTVTLLG VTVTVCRSFIPDQHMVFCPEQLLRVILA HIHYMPDHWQGNAHRSQTRDEFAQLF QYKAVFILEELLSPIVTPLILIFCLRPRAL EIIDFFRNFTVEVVGVGDTCSFAQMDV RQHGHPQWLSAGQTEASVYQQAEDGK TELSLMHFAITNPGWQPPRESTAFLGFL KEQVQRDGAAASLAQGGLLPENALFTS IQSLQSESEPLSLIANVVAGSSCRGPPLP RDLQGSRHRAEVASALRSFSPLQPGQA PTGRAHSTMTGSGVDARTASSGSSVWE GQLQSLVLSEYASTEMSLHALYMHQLH KQQAQAEPERHVWHRRESDESGESAP DEGGEGARAPQSIPRSASYPCAAPRPGA PETTALHGGFQRRYGGITDPGTVPRVPS HFSRLPLGGWAEDGQSASRHPEPVPEE GSEDELPPQVHKV 12  APG10L NP_113670 MEEDEFIGEKTFQRYCAEFIKHSQQIGD 202 S116 SWEWRPSKDCSDGYMCKIHFQIKNGSV MSHLGASTHGQTCLPMEEAFELPLDDC EVIETAAASEVIKYEYHVLYSCSYQVPV LYFRASFLDGRPLTLKDIWEGVHECYK MRLLQGPWDTITQQEHPILGQPFFVLHP CKTNEFMTPVLKNSQKINKNVNYITSW LSIVGPVVGLNLPLSYAKATSQDERNVP 13  APG12L NP_004698 MTSREHQVSLCNCVPLLRRLLCDAPWR 203 S26, S41 KARPLHALSRYFRSRVSPSKMAEEPQS VLQLPTSIAAGGEGLTDVSPETTTPEPPS SAAVSPGTEEPAGDTKKKIDILLKAVGD TPIMKTKKWAVERTRTIQGLIDFIKKFL KLVASEQLFIYVNQSFAPSPDQEVGTLY ECFGSDGKLVLHYCKSQAWG 14  APG16L NP_110430 MSSGLRAADFPRWKRHISEQLRRRDRL 204 S287, S304 QRQAFEEIILQYNKLLEKSDLHSVLAQK LQAEKHDVPNRHEISPGHDGTWNDNQ LQEMAQLRIKHQEELTELHKKRGELAQ LVIDLNNQMQRKDREMQMNEAKIAEC LQTISDLETECLDLRTKLCDLERANQTL KDEYDALQITFTALEGKLRKTTEENQEL VTRWMAEKAQEANRLNAENEKDSRRR QARLQKELAEAAKEPLPVEQDDDIEVIV DETSDHTEETSPVRAISRAATKRLSQPA GGLLDSITNIFGRRSVSSFPVPQDNVDT HPGSGKEVRVPATALCVFDAHDGEVN AVQFSPGSRLLATGGMDRRVKLWEVF GEKCEFKGSLSGSNAGITSIEFDSAGSYL LAASNDFASRIWTVDDYRLRHTLTGHS GKVLSAKFLLDNARIVSGSHDRTLKLW DLRSKVCIKTVFAGSSCNDIVCTEQCV MSGHFDKKIRFWDIRSESIVREMELLGK ITALDLNPERTELLSCSRDDLLKVIDLRT NAIKQTFSAPGFKCGSDWTRVVFSPDG SYVAAGSAEGSLYIWSVLTGKVEKVLS KQHSSSINAVAWSPSGSHVVSVDKGCK AVLWAQY 15  BECN1 NP_003757 MEGSKTSNNSTMQVSFVCQRCSQPLKL 205 S64, T72, DTSFKILDRVTIQELTAPLLTTAQAKPG S249 ETQEEETNSGEEPFIETPRQDGVSRRFIP PARMMSTESANSFTLIGEASDGGTMEN LSRRLKVTGDLFDIMSGQTDVDHPLCE ECTDTLLDQLDTQLNVTENECQNYKRC LEILEQMNEDDSEQLQMELKELALEEE RLIQELEDVEKNRKIVAENLEKVQAEA ERLDQEEAQYQREYSEFKRQQLELDDE LKSVENQMRYAQTQLDKLKKTNVFNA TFHIWHSGQFGTINNFRLGRLPSVPVEW NEINAAWGQTVLLLHALANKMGLKFQ RYRLVPYGNHSYLESLTDKSKELPLYC SGGLRFFWDNKFDHAMVAFLDCVQQF KEEVEKGETRFCLPYRMDVEKGKIEDT GGSGGSYSIKTQFNSEEQWTKALKFML TNLKWGLAWVSSQFYNK APG8b microtubule- NP_001001169.1 MPSEKTFKQRRTFEQRVEDVRLIREQHP 206 associated TKIPVIIERYKGEKQLPVLDKTKFLVPD protein 1 HVNMSELIKIIRRRLQLNANQAFFLLVN light chain 3 GHSMVSVSTPICEVYESEKDEDGFLYM beta [Bos VYASQETFGMKLSV taurus] APG10L hypothetical NP_001032201.1 MMTGERKPASCFLDENTFRLCCRLFLQ 207 protein HSESIQDGWIWEQIKGSDEGFMKKTVLI LOC641330 PVKSSLLDKQHESIQAENTELPTDDFEA [Danio DAEDETAGVDAVCESHAVLRYEYHVL rerio] YSCSYQIPVLYFRASALDGRSLSLEEVW SNVHPNYRQRLKQEPWDTLTQQEHPLL GQPFFMLHPCRTEEFMKPALELAHAQN RRVNYIVSWLSVVGPVVGLDVPLSFST AVSAPD APG10L autophagy- NP_080046.3 MEDEFFGEKSFQHYCAEFIRHSQQIGDG 208 related 10- WEWRTAKECSDGYMCKTQFRIKNETL like [Mus TPHASVLTCLPTEENLELPMDDSEVTRP musculus] AAVAEVIKHEYHVLYSCSYQVPVLYFR ASFLDGRPLALEDIWEGVHECYKPRLL QGPWDTITQQEHPILGQPFFVLHPCKTN EFMTAVLKNSQKINRNVNYITSWLSLV GPVVGLNLPLSYAKATSQSE APG10L PREDICTED: XP_001067400.1 MEDEFFGEESFQHCCAEFIRHSQQIGDG 209 similar WEWRTAKECSDGYMCKTQFQIKKETP to TPHRETPASVHTCLPTEENLELPVDDSE autophagy- AVGPAAAAVIRQEYHVLYSCSYQVPVL related 10- YFRASFLDGRPLALEDIWEGVHECYKL like [Rattus RLLQGPWDTITQQEHPILGQPFFVLHPC norvegicus] KTNEFMTAVLKNSQKINRNVNYITSWL SIVGPVVGLNLPLSYAKATSQSE APG10L PREDICTED: XP_517669.1 MEEDEFIGEKTFQRYCAEFIKHSQQIGD 210 hypothetical SWEWRPSKDCSDGYMCKIHFQIKNGSV protein [Pan MSHLGASTHGQTCLPMEEAFELPLDDC troglodytes] EVIETAAASEVIKYEYHVLYSCSHQVPV LYFRASFLDGRPLTLKDIWEGVHECYK MRLLQGPWDTITQQEHPILGQPFFVLHP CKTNEFMTPVLKNSQKINKNVNYITSW LSIVGPVVGLNLPLSYAKATSQDERNVH APG10L PREDICTED: XP_852603.1 MEEDEFFGEKTFQHFCAEFIKHSQQIGD 211 similar GWEWRTSKDCSEGYMCKTHFQIKPGM to APG10 PMSPPGTSAHIQTCLPMEEALELPLDDF autophagy EKTETTTGSEVIKYEYHVLYSCSYQVPV 10-like LYFRASFLDGRPLALKDIWEGTHECYK [Canis TRLLQEPWDTITQQEHPILGQPFFVLHP familiaris] CKTNEFMTPVLKNSRKINRSVNYITSW LSVVGPVVGLNLPLSYARTASQDEGNVN APG10L PREDICTED: XP_869807.2 MEENEFFGEKTFQHYCAEFIKHSQKIGD 212 hypothetical GWEWRASKDCSDGYMCKTHFQVKNG protein [Bos TAVSHQGTSDHVQTFLPVEEALDPPLD taurus] DLEVNETTTAAEVIKYEYHVLYSCSYQ VPVLYFRASFLDGRPLALKDIWEGVHE CYKMRLLQGPWDTITQQDKRVHRKNQ GSTTKTAALVWSLTKRVKGLLRSNFPN YKHKVPTPPHAVALGLSLSASEPAPRV CSERLRRAPGSCKGFWDW APG12 APG12 NP_004698.2 MTSREHQVSLCNCVPLLRRLLCDAPWR 213 autophagy KARPLHALSRYFRSRVSPSKMAEEPQS 12-like VLQLPTSIAAGGEGLTDVSPETTTPEPPS [Homo SAAVSPGTEEPAGDTKKKIDILLKAVGD sapiens] TPIMKTKKWAVERTRTIQGLIDFIKKFL KLVASEQLFIYVNQSFAPSPDQEVGTLY ECFGSDGKLVLHYCKSQAWG APG12L autophagy NP_001033584.1 MAEDPEAVLQLPAAPAAAAGESLLELS 214 12-like PETAIPEPPSSVAVSPGTEEPPGDTKKKI [Rattus DILLKAVGDTPIMKTKKWAVERTRTVQ norvegicus] ALIDFIRKFLRLLASEQLFIYVNQSFAPS PDQEVGTLYECFGSDGKLVLHYCKSQA WG APG12L ATG12 NP_001070450.1 MAEEQESALQLPPSTAPEAEVPTEVSPE 215 autophagy TATPEPPSSAAVSPGTEEPVGDTKKKIDI related 12 LLKAVGDTPIMKTKKWAVERTRTIQGL homolog FDFIKKFLKLVASEQLFIYVNQSFAPSPD [Bos taurus] QEVGTLYECFGSDGKLVLHYCKSQAWG APG12L autophagy- NP_080493.2 MSEDSEVVLQLPSAPVGAGGESLPELSP 216 related 12- ETATPEPPSSAAVSPGTEEPPGDTKKKI like [Mus DILLKAVGDTPIMKTKKWAVERTRTIQ musculus] GLIDFIKKFLKLVASEQLFIYVNQSFAPS PDQEVGTLYECFGSDGKLVLHYCKSQA WG APG12L PREDICTED: XP_001167385.1 MVEEPQSMLQLPPSSATGEEGLTEVSPE 217 hypothetical TTTLEPPSSAAVSPGTEEPAGDTKKKIDI protein [Pan LLKAVGDTPIMKTKKWAVE troglodytes] APG12L PREDICTED: XP_424963.1 MAEAEEQAPVSPQSEGRSGAGEEAPER 218 hypothetical TPESGASLGVGEPATSPAGSPGTEDPAG protein DAKKKIDVLLKAVGDTPIMKTKKWAV [Gallus ERTRTIQGLCDFIKKFLKLMASEQLFIY gallus] VNQSFAPSPDQEVGTLYECFGSDGKLV LHYCKSQAWG APG12L PREDICTED: XP_531866.2 MAEESESGLQLPPSTAAEGEGPTEVSPE 219 similar TATPEPPSSAAVSPGTEEPAGDTKKKID to VLLKAVGDTPIMKTKKWAVERTRTIQG Autophagy LIDFIKKFLKLVASEQLFIYVNQSFAPSP protein 12- DQEVGTLYECFGSDGKLVLHYCKSQA like WG (APG12- like) (ATG12) isoform 1 [Canis familiaris] APG16L ATG16 NP_001017854.1 MAGRRVECLWKRHVVEQLKQRDRVQ 220 autophagy RQAFEEIIHQYNRLLEKSDLQVVFSERL related 16- QTEKYEQQNRHDLSPCVDGGRSDSLQQ like 1 EMSQMRIRHQEELTELHKKRGELAQSV [Danio IELNNQIQQKDKEIQSNEVKMQEYLQQI rerio] SQLEGECRELRNCLADLERANQTLRDE YDALQITFSALEEKLRKTTEDNQELVTR WMAEKAQEANRLNAENEKDSRRRQA KLQKELADAAKEPLPIDPDDDIEVLTED AGKATGETSPSRQLSRTPSKRLSQPPPP AGLLDSISNMFGRRRSVNSFSSSPENAE VPSACADVRVPSTALHIFDAHDGEVNA VICR APG16L APG16L NP_084122.2 MSSGLRAADFPRWKRHIAEELRRRDRL 221 beta isoform QRQAFEEIILQYTKLLEKSDLHSVLTQK [Mus LQAEKHDMPNRHEISPGHDGAWNDSQ musculus] LQEMAQLRIKHQEELTELHKKRGELAQ LVIDLNNQMQQKDKEIQMNEAKISEYL QTISDLETNCLDLRTKLQDLEVANQTL KDEYDALQITFTALEEKLRKTTEENQEL VTRWMAEKAQEANRLNAENEKDSRRR QARLQKELAEAAKEPLPVEQDDDIEVIV DETSDHTEETSPVRAVSRAATKRLSQP AGGLLDSITNIFGRRSVSSIPVPQDIMDT HPASGKDVRVPTTASYVFDAHDGEVN AVQFSPGSRLLATGGMDRRVKLWEAF GDKCEFKGSLSGSNAGITSIEFDSAGAY LLAASNDFASRIWTVDDYRLRHTLTGH SGKVLSAKFLLDNARIVSGSHDRTLKL WDLRSKVCIKTVFAGSSCNDIVCTEQC VMSGHFDKKIRFWDIRSESVVREMELL GKITALDLNPERTELLSCSRDDLLKVID LRTNAVKQTFSAPGFKCGSDWTRVVFS PDGSYVAAGSAEGSLYVWSVLTGKVE KVLSKQHSSSINAVAWAPSGLHVVSVD KGSRAVLWAQP APG16L PREDICTED: XP_343620.3 MSSGLRAADFPRWKRHIAEELRRRDRL 222 similar QRQAFEEIILQYTKLLEKSDLHSVLTQK to APG16L LQAEKHDVPNRHEISPGHDGAWNDSQL beta isoform QEMAQLKMKHQEELTELHKKRGELAQ [Rattus LVIDLNNQMQQKDKEIQTNEAKIAECL norvegicus] QTISDLEADCLDLRTKLQDLEVANQTL KDEYDALQITFTALEEKLRKTTEENQEL VTRWMAEKAQEANRLNAENEKDSRRR QARLQKELAEAAKEPLPVEQDDDIEVIV DETSDHTEETSPVRAISRAATRRSVSSIP VPQDVVDTHPASGKDVRVPTTASYVFD AHDGEVNAVQFSPGSRLLATGGMDRR VKLWEAFGDKCEFKGSLSGSNAGITSIE FDSAGAYLLAASNDFASRIWTVDDYRL RHTLTGHSGKVLSAKFLLDNARIVSGS HDRTLKLWDLRSKVCIKTVFAGSSCND IVCTEQCVMSGHFDKKIRFWDIRSESVV REMELLGKITALDLNPERTELLSCSRDD LLKIIDLRTNAIKQSFSAPGFKCGSDWT RVVFSPDGSYVAAGSADGSLYVWSVL TGKVEKVLSKQHSSSINAVAWAPSGLH VVSVDKGSRAVLWAQP APG16L PREDICTED: XP_422568.2 MASGLHAAGFPPWKRHIAAELRRRDRL 223 similar QRQAFEEIVAQYNKLLEKSDLHAVLAD to APG16L KLQAEKYDMQSRHEISPGHDGTWNDA beta [Gallus QLQELAQLKIKHQEELTELHKKRGELA gallus] QSVIDLNNQMQQKDKEMQMNEAKIAE YLQKISELETECQELRSKLQDLERANQT LKDEYDALQITFNALEEKLRKTTEDNQ ELVSRWMAEKAQEANRLNAENEKDSR RRQARLQKELAEAAKEPLPVEPDDDIE VLADETSDTAEETSPVRAVSRTPSKRLS QPAGGLLDSITNIFGRRSLSSFPPPQDNA EPHPGASKEVRVPTTAICVFDAHDGEV NAVQFSPGSRLLATGGMDRRVKLWEV LGDRCEPKGSLSGSNAGITSIEFDSAGS YLLAASNDFASRIWTVDDNRLRHTLTG HSGKVLSAKFLLDNARIVSGSHDRTLK LWDLRSKVCIKTVFAGSSCNDIVCTEQ CVMSGHFDKKIRFWDIRTESIVKELELL GRITALDLNSERTELLTCSRDDLLKIIDL RVGAVKQTFSAQGFKCGSDWTRVVFS PDGNYVAAGSADGALYVWNVLTGKLE RTLAKHHSSPINAVAWSPAGAHVVSVD KGNKAVLWSEF APG16L PREDICTED: XP_862068.1 MSSGLRAADFPRWKRHISEELRRRDRL 224 similar QRQAFEEIILQYNKLLEKSDLHSVLAHK to LQAEKHDIPNRHEISPGHDGAWNDGQL Autophagy QEMAQLRIRHQEELTELHKKRGELAQL protein 16- VIDLNNQMQQKDREMQMNEAKIAECL like QTISDLETECQELRSKLQDLERANQTLK (APG16- DEYDALQITFTALEEKLRKTTEENQELV like) TRWMAEKAQEANRLNAENEKDSRRRQ isoform 3 ARLQKELAEAAKEPLPVEQDDDIEVIVD [Canis ETSDHAEETSPVRAISRAATKRLSQPAG familiaris] GLLDSITNIFGLSESPLLGHHSSDAARRR SVSSFPVPQDNVDTHPGSSKEVRVPTTA MCIFDAHDGEVNAVQFSPGSRLLATGG MDRRVKLWEVFGDKCEFKGSLSGSNA GITSIEFDSAGSYLLAASNDFASRIWTV DDYRLRHTLTGHSGKVLSAKFLLDNAR IVSGSHDRTLKLWDLRSKVCIKTVFAGS SCNDIVCTEQCVMSGHFDKKIRFWDIRS ESIVREMELLGKITALDLNPERTELLSCS RDDLLKIIDLRINAVRQTFSAPGFKCGS DWTRVVFSPDGGYVAAGSAEGSLYIW SVLSGKVEKVLSKQHGSSINAVAWSPS GSHVVSVDKGSKAVLWSEY APG16L PREDICTED: XP_877095.2 MSSGLRAAVFPRWKRHISEELRRRDRL 225 similar QRQAFEEIILQYNKLLEKSDLHSVLAHK to APG16L LQAEKHDVPNRHEISPGHDGSWNDSQL beta isoform QEMAQLRIKHQEELTELHKKRGELAQL 5 [Bos VIDLNNQMQQKDKEMQMNEAKIAEYL taurus] QTISDLETECQELRTKLQDLERANQTLK DEYDALQITFTALEEKLRKTSEENQELV TRWMAEKAQEANRLNAENEKDSRRRQ ARLQKELAEAAKEPLPVEQDDDIEVLV DETSEHPEETSPVRAISRAATKRLSQPA GGLLDSITNIFGRRSVSSFPVPQDNVDP HPGAGKEVRVPTTAMSVFDAHDGEVN AVQFSPGSRLLATGGMDRRVKLWEVF GDKCEFKGSLSGSNAGITSIEFDSAGSY LLAASNDFASRIWTVDDYRLRHTLTGH SGKVLSAKFLLDNARIVSGSHDRTLKL WDLRSKVCIKTVFAGSSCNDIVCTEQC VMSGHFDKKIRFWDIRSESIVREMELLG KITALDLNPERTELLSCSRDDLLKIIDLRI NAVRQTFSAPGFKCGSDWTRAVFSPDG SYVAAGAAEGSLYIWNVLSGKVEKVLS KHHSSSINAVAWSPAGSHVVTVDKGSK AVLWSEY APG3 Apg3p NP_071933.2 MQNVINTVKGKALEVAEYLTPVLKESK 226 [Homo FKETGVITPEEFVAAGDHLVHHCPTWQ sapiens] WATGEELKVKAYLPTGKQFLVTKNVP CYKRCKQMEYSDELEAIIEEDDGDGGW VDTYHNTGITGITEAVKEITLENKDNIR LQDCSALCEEEEDEDEGEAADMEEYEE SGLLETDEATLDTRKIVEACKAKTDAG GEDAILQTRTYDLYITYDKYYQTPRLW LFGYDEQRQPLTVEHMYEDISQDHVKK TVTIENHPHLPPPPMCSVHPCRHAEVM KKIIETVAEGGGELGVHMYLLIFLKFVQ AVIPTIEYDYTRHFTM APG3L ATG3 NP_001068832.1 MQNVINTVKGKALEVAEYLTPVLKESK 227 autophagy FKETGVITPEEFVAAGDHLVHHCPTWQ related 3 WATGEELKVKAYLPSGKQFLVTKNVP homolog CYKRCKQMEYSDELEAIIEEDDGDGGW [Bos taurus] VDTYHNTGIAGITEAVKEITLESKDSIKL QDCSALCEEEEEEDEGEAADMEEYEES GLLETDEATLDTRKIVEACKAKTDAGG EDAILQTRTYDLYITYDKYYQTPRLWL FGYDEQRQPLTVEHMYEDISQDHVKKT VTIENHPHLPPPPMCSVHPCRHAEVMK KIIETVAEGGGELGVHMYLLIFLKFVQA VIPTIEYDYTRHFTM APG3L autophagy NP_080678.1 MQNVINTVKGKALEVAEYLTPVLKESK 228 Apg3p/Aut1 FKETGVITPEEFVAAGDHLVHHCPTWQ p-like [Mus WATGEELKVKAYLPTDKQFLVTKNVP musculus] CYKRCKQMEYSDELEAIIEEDDGDGGW VDTYHNTGITGITEAVKEITLESKDSIKL QDCSALCDEEDEEDEGEAADMEEYEES GLLETDEATLDTRKIVEACKAKADAGG EDAILQTRTYDLYITYDKYYQTPRLWL FGYDEQRQPLTVEHMYEDISQDHVKKT VTIENHPHLPPPPMCSVHPCRHAEVMK KIIETVAEGGGELGVHMYLLIFLKFVQA VIPTIEYDYTRHFTM APG3L autophagy- NP_599221.1 MQNVINTVKGKALEVAEYLTPVLKESK 229 related 3 FKETGVITPEEFVAAGDHLVHHCPTWQ [Rattus WATGEELKVKAYLPTGKQFLVTKNVP norvegicus] CYKRCKQMEYSDELEAIIEEDDGDGGW VDTYHNTGITGITEAVKEITLESKDSIKL QDCSVLCDEEEEEEEGEAADMEEYEES GLLETDEATLDTRRIVEACKAKADAGG EDAILQTRTYDLYITYDKYYQTPRLWL FGYDEQRQPLTVEHMYEDISQDHVKKT VTIENHPHLPPPLMCSVHPCRHAEVMK KIIETVAEGGGELGVHMYLLIFLKFVQA VIPTIEYDYTRHFTM APG3L Aut1 NP_649059.1 MQSVLNTVKGTALNVAEYLTPVLKESK 230 CG6877-PA FRETGVLTPEEFVAAGDHLVHHCPTWQ [Drosophila WAAGDETKTKPYLPKDKQFLITRNVPC melanogaster] YRRCKQMEYVGEETLVEEESGDGGWV ETHQLNDDGTTQLEDKICELTMEETKE EMHTPDSDKSAPGAGGQAEDEDDDEAI DMDDFEESGMLELVDPAVATTTRKPEP EAKASPVAAASGDAEASGDSVLHTRTY DLHISYDKYYQTPRLWVVGYDEQRKPL TVEQMYEDVSQDHAKKTVTMESHPHL PGPNMASVHPCRHADIMKKIIQTVEEG GGQLGVHLYLIIFLKFVQTVIPTIEYDFT QNFNMS APG3L APG3 NP_956316.1 MQNVINSVKGTALGVAEFLTPVLKESK 231 autophagy FKETGVITPEEFVAAGDHLVHHCPTWK 3-like WASGEEAKVKPYLPNDKQFLLTRNVPC [Danio YKRCKQMEYSDELEAIIEEDDGDGGWV rerio] DTFHNSGVTGVTEAVREISLDNKDNMN MNVKTGACGNSGDDDDDEEGEAADM EEYEESGLLETDDATLDTSKMADLSKT KAEAGGEDAILQTRTYDLYITYDKYYQ TPRLWLFGYDEDRQPLTVDQMYEDISQ DHVKKTVTIENHPNLPPPAMCSVHPCR HAEVMKKIIETVAEGGGELGVHMYLLI FLKFVQAVIPTIEYDYTRHFTM APG3L PREDICTED: XP_001155234.1 MQNVINTVKGKALEVAEYLTPVLKESK 232 hypothetical FKETGVITPEEFVAAGDHLVHHCPTWQ protein WATGEELKVKAYLPTGKQFLVTKNVP isoform 1 CYKRCKQMEYSDELEAIIEEDDGDGGW [Pan VDTYHNTGITGITEAVKEITLENKDNIR troglodytes] LQDCSALCEEEEDEDEGEAADMEEYEE SGLLETDEATLDTRKIVEACKAKTDAG GEDAILQTRTYDLYITYDKYYQTPRLW LFGYDEQRQPLTVEHMYEDISQDHVKK TVTIENHPHLPPPPMCSVHPCRHAEVM KKIIETVAEGGGELGVHMYLLIFLKFVQ AVIPTIEYDYTRHFTM APG3L AGAP011582- XP_309926.3 MQNVLNSVKGTALGVAEYLTPVLKES 233 PA KFRETGVLTPEEFIAAGDHLTHHCPTWS [Anopheles WAVGDESKIKPYLPKDKQFLITRNVPC gambiae str. RRRCKQIEFVGEENLVEENDPDGGWVE PEST] THHYNPDEAGSSGLEDKVCEMKLDSSR IEDEPAADMDDPRNLEDGDGDGGQDD DEDGAAIDMDEFEESGLLEMVDPSNAL LPAPNEKPKPTVAASETEGDSVVRTRT YDLHITYDKYYQTPRLWVIGYDENRKL LSVEQMYDDVSQDHAKKTVTMETHPH LPGPNMASVHPCKHADIMKKIIQTVEE GGGELGVHMYLIIFLKFVQTVIPTIEYDF TQNFNITNHK APG3L PREDICTED: XP_416588.1 MQNVINTVKGKALEVAEYLTPVLKESK 234 hypothetical FKETGVITPEEFVAAGDHLVHHCPTWQ protein WASGEELKVKAYLPTDKQFLVTKNVP [Gallus CYKRCKQMEYSDEQEAIIEEDDGDGG gallus] WVDTFHNAGIVGATEAVKEITLDSKDN IKIPERSASCEDDDDEDEGEAADMEEYE ESGLLETDDATLDTRQIVEVKAKVDVG GEDAILQTRTYDLYITYDKYYQTPRLW LFGYDEQRQPLTVEHMYEDISQDHVKK TVTIENHPHLPPPPMCSVHPCRHAEVM KKIIETVAEGGGELGVHMYLLIFLKFVQ AVIPTIEYDYTRHFTM APG3L PREDICTED: XP_535740.2 MCINTVKGKALEVAEYLTPVLKESKFK 235 similar ETGVITPEEFVAAGDHLVHHCPTWQW to Apg3p ATGEELKVKAYLPTGKQFLVTKNVPCY [Canis KRCKQMEYSDELEAIIEEDDGDGGWVD familiaris] TYHNAGVTGITEAVKEITLESKDSIKLQ DCSAVCEEEEEEDEGEAADMEEYEESG LLETDEATLDTRKIVEACKAKTDAGGE DAILQTRTYDLYITYDKYYQTPRLWLF GYDEQRQPLTVEHMYEDISQDHVKKT VTIENHPHLPPPPMCSVHPCRHAEVMK KIIETVAEGGGELGVHMYLLIFLKFVQA VIPTIEYDYTRHFTM APG4A autophagy- NP_001001171.1 MESVLSKYENQITIFADYLEEFPDTDEL 236 related VWILGKQHLLKTEKSKLLSDISARLWFT cysteine YRRKFSPIGGTGPSSDAGWGCMLRCGQ endopeptidase MMLAQALICRHLGRDWNWEKQKEQP 2 [Bos KEYQRILQCFLDRKDCCYSIHQMAQMG taurus] VGEGKSIGEWFGPNTVAQVLKKLALFD EWNSLAVYVSMDNTVVIEDIKKMCRTL SLSADTPAERPLESLTASNQSKGPSACC TAWKPLLLIVPLRLGINQINPVYVDAFK ECFKMPQSLGALGGKPNNAYYFIGFLG DELIFLDPHTTQTFVDTEENGTADDQTF HCLQPPQRMNILNLDPSVALGFFCKEE KDFDSWCSLVQKEILKENLRMFELVQK HPSHWPPFVPPAKPEVTTTGAEFIDSTE QLEEFDLEEDFEILSI APG4A hypothetical NP_001019605.1 MEAVLAKYENQINVFLEDLPDTDEPVW 237 protein ILGACYNVKTKKSELLSDVRSRLWFTY LOC554140 RKKFSPIGGTGPSSDAGWGCMLRCGQ [Danio MILAQALICSHLGRDWRWDPEKHQPKE rerio] YQRILDCFLDKKDSCYSIHQMAQMGV GEGKSVGEWYGPNTVAQVLKKLALFD DWNSLSVYVSMDNTVVIEDIKKLCVRA DLQLQSQQPLDWRPLLLVIPLRMGINSI NPVYIQALKECFKMPQSCGVLGGKPNL AYYFIGFIDDELIYLDPHTTQQAVDTES GSAVDDQSFHCQRTPHRMKITSLDPSV ALGFFCKSEEDFDSWCDLVQQELLKKR NLRMFELVEKHPSHWPPFVPPTKPEVQ TTGAEFIESPDKLSESEEEFEILNA APG4A AuTophaGy NP_493375.1 MTEEILKQGVGIVETSLTFEPPFCESFER 238 (yeast Atg ISIDNFPIFALGKEISKEDGIEAMKKYVT homolog) SRFWFTYRRDFSPIGGTGPSTDQGWGC family MLRCAQMLLGEVLLRRHIGRHFEWDIE member KTSEIYEKILQMFFDEKDALYSIHQIAQ (atg-4.1) MGVTEGKEVSKWFGPNTAAQVMKKLT [Caenorhabditis IFDDWSNIAVHVALDNILVKEDAITMAT elegans] SYPSEDAVKLIMGKKGLQTTKRKNRKN LDFTVKYLKQIKFFKFFNLFQIFYENGL VDKNRLSLSPGNIIPEWRPLLLMIPLRLG LTTINPCYLSAIQEFFKIPQCVGIIGGRPN HALYFVGMSGSKLFYLDPHYCRPKTES TAKMYAEKDSTATTDDVGFSHLEELVP LPSQTADVYTKMDDSTYHCQMMLWIE YENVDPSLALAMFCETRDEFENLCETL QKTTLPASQPPMFEFLQRRPKYLPKFEP YTGVSMKIEMKEFDDIGAANVKIDDDF EVLDVHTEEEDADEDNDDDVANA APG4A autophagy- NP_777364.3 MESVMSKYENQILIFPDYLEEFPDTDEL 239 related 4A- VWILGKQHPLKTEKSKLLSDISARLWFT like [Mus YRRKFSPIGGTGPSSDAGWGCMLRCGQ musculus] MMLAQALICRHLGRDWNWERQKEQP KEYQRILQCFLDRKDCCYSIHQMAQMG VGEGKSIGEWFGPNTVAQVIKKLALFD EWNSLAVYVSMDNTVVIEDIKKMCCV LPVGAADPAGDFLTASNQSRDTSVPCS AWKPLLLIVPLRLGINQINPVYVEAFKE CFKMPQSLGALGGKPNNAYYFIGFLGD ELIFLDPHTTQTFVDIEESGLVDDQTFHC LQSPQRMSILNLDPSVALGFFCKEEKDF DNWCSLVQKEILKENLRMFELVQKHPS HWPPFVPPAKPEVTTTGAEFIESTEQLE DFELEEDFEILSVG APG4A PREDICTED: XP_529098.2 MESVLSKYEDQITIFTDYLEEYPDTDEL 240 autophagy- VWILGKQHLLKTEKSKLLSDISARLWFT related YRRKFSPIGGTGPSSDAGWGCMLRCGQ cysteine MMLAQALICRHLGRDWSWEKQKEQPK endopeptidase EYQRILQCFLDRKDCCYSIHQMAQMGV 2 isoform GEGKSIGEWFGPNTVAQVLKKLALFDE 8 [Pan WNSLAVYVSMDNTVVIEDIKKMCRVL troglodytes] PLSIDTPGDRPPDSLTASNQSKGTSAYC SAWKPLLLIVPLRLGINQINPVYVDAFK ECFKMPQSLGALGGKPNNAYYFIGFLG DELIFLDPHTTQTFVDTEENGTVNDQTF HCLQSPQRMNILNLDPSVALGFFCKEE KDFDNWCSLVQKEILKENLRMFELVQK HPSHWPPFVPPAKPEVTTTGAEFIDSTE QLEEFDLEEDFEILSV APG4A PREDICTED: XP_538136.2 MTANQKSGRLWELQFERSSGWRGAFT 241 similar VLTDSAPSSAELQVPGSLAAAVVKCRV to ELAQDDSWRMESVLSKYENQITIFADY autophagy- LEEFPDSDELVWILGKQHLLKTEKSKLL related SDIRARLWFTYRRKFSPIGGTGPSSDAG cysteine WGCMLRCGQMMLAQALICRHLGRDW endopeptidase SWEKQKEQPREYQRILQCFLDRKDCCY 2 isoform SIHQMAQMGVGEGKSIGEWFGPNTVA a [Canis QVLKKLALFDEWNSLAIYVSMDNTVVI familiaris] EDIKKMCCVLPLSADTIGESPLNTLNAS NQSKSAPASCPAWKPLLLIVPLRLGINQ INPVYVDAFKECFKMPQSLGALGGKPN NAYYFIGFLGDELIFLDPHTTQTFVDTE ENGTVDDQTFHCLQSPQRMNILNLDPS VALGFFCKEEKDFDSWCSLVQKEILKE NLRMFELVQKHPSHWPPFVPPAKPEVT TTGAEFIDSTEQLEDFDLEEDFEILSV APG4B APG4 NP_001001170.1 MDAATLTYDTLRFAEFEDFPETSEPVWI 242 autophagy 4 LGRKYSVLTEKDEILADVASRLWFTYR homolog B KNFPAIGGTGPTSDTGWGCMLRCGQMI [Bos taurus] FAQALVCRHLGRDWRWTQRKRQPDSY CSVLQAFLDRKDSCYSIHQIAQMGVGE GKSIGQWYGPNTVAQVLKKLAVFDTW SALAVHVAMDNTVVMADIRRLCRSSLP CAGAEAFPADSERHCNGFPAGAEGGGR AAPWRPLVLLIPLRLGLADVNAAYAGT LKHCFRMPQSLGVIGGKPNSAHYFIGY VGEELIYLDPHTTQPAVAAADRCPVPD ESFHCQHPPGRMSIAELDPSIAVGFFCET EDDFNDWCQQVSKLSLLGGALPMFEL VEQQPSHLACPDVLNLSLDSSDAERLE RFFDSEDEDFEILSL APG4B autophagin NP_777363.1 MDAATLTYDTLRFAEFEDFPETSEPVWI 243 1 [Mus LGRKYSIFTEKDEILSDVASRLWFTYRR musculus] NFPAIGGTGPTSDTGWGCMLRCGQMIF AQALVCRHLGRDWRWTQRKRQPDSYF NVLNAFLDRKDSYYSIHQIAQMGVGEG KSIGQWYGPNTVAQVLKKLAVFDTWS SLAVHIAMDNTVVMEEIRRLCRANLPC VGAAALPTDSERHCNGFPAGAEVTNRP SAWRPLVLLIPLRLGLTDINEAYVETLK HCFMMPQSLGVIGGKPNSAHYFIGYVG EELIYLDPHTTQPAVELTDSCFIPDESFH CQHPPSRMGIGELDPSIAVGFFCKTEED FNDWCQQVKKLSQLGGALPMFELVEQ QPSHLACQDVLNLSLDSSDVERLERFFD SEDEDFEILSL APG4B APG4 NP_998738.1 MDAATLTYDTLRFEYEDFPETKEPVWI 244 autophagy 4 LGRKYSVFTEKEEILLDVTSRLWFTYRK homolog B NFPAIGGTGPTSDTGWGCMLRCGQMIF [Gallus AQALVCRHLGRDWRWIKGKRQTDNYF gallus] SVLNAFIDKKDSYYSIHQIAQMGVGEG KSIGQWYGPNTVAQVLKKLATFDTWSS LAVHIAMDNTVVMEEIRRLCQSNFSCA GAAACPAVEADVLYNGYPEEAGVRDK LSLWKPLVLLIPLRLGLTEINEAYIETLK HCFMMPQSLGVIGGKPNSAHYFIGYVG EELIYLDPHTTQPAVEPSDSGCLPDESF HCQHPPCRMSIAELDPSIAVGFFCHTEE DFNDWCHQIKKLSLVRGALPMFELVER QPSHFSNPDVLNLTPDSSDADRLERFFD SEDEDFEILSL APG4B PREDICTED: XP_001162556.1 MLRCGQKIFAQALVCRHLGRDWRWTQ 245 similar RKRQPDSYFSVLNAFIDRKDSYYSIHQI to APG4 AQMGVGEGKSIGQWYGPNTVAQVLKK autophagy 4 LAVFDTWSSLAVHIAMDNTVVMEEIRR homolog B LCRTSVPCAGATAFPADSDRHCNGFPA isoform b GAEVTNRLSPWRPLVLLIPLRLGLTDIN [Pan EAYVETLKHCFMMPQSLGVIGGKPNSA troglodytes] HYFIGYVGEELIYLDPHTTQPAVEPTDG CFIPDESFHCQHPPCRMSIAELDPSIAVG FFCKTEDDFSDWCQQVKKLSLLGGALP MFELVEQQPSHLACPDVLNLSLGESCQ VQILLM APG4B PREDICTED: XP_851977.1 MLTDATLTYDTLRFAEFEDFPETSEPV 246 similar WILGRKYSIFTEKDEILSDVASRLWFTY to Cysteine RKNFPAIGGTGPTSDTGWGCMLRCGQ protease MIFAQALVCRHLGRDWRWTQRKRQPD APG4B SYFNVLNAFIDRKDSYYSIHQIAQMGV (Autophagy GEGKSIGQWYGPNTVAQVLKKLAVFD 4 homolog TWSALAVHIAMDNTVVMEDIRRLCRGS B) LPCAGAAALPADSSRHCNGFPAGAEVT (hAPG4B) NRLAPWRPLVLLIPLRLGLTDINEAYVE (Autophagin- TLKRCFMMPQSLGVIGGKPNSAHYFIG 1) YVGEELIYLDPHTTQPAVEFTDSCFIPDE (Autophagy- SFHCQHPPSRMSIGELDPSIAVGFFCKTE related GDFDDWCQQVRQLSLLGGALPMFELV cysteine EQQPSHLACPDVLNLSLDSSDVERLERF endopeptidase FDSEDEDFEILSL 1) (AUT- like 1 cysteine endopeptidase) [Canis familiaris] APG4C APG4 NP_778194.2 MEASGTDEVDKLKTKFISAWNNMKYS 247 autophagy 4 WVLKTKTYFSRNSPVLLLGKCYHFKYE homolog C DESKMLPARSGCAIEDHVIAGNVEEFR [Mus KDFISRLWLTYREEFPQIEASALTTDCG musculus] WGCTLRTGQMLLAQGLILHFLGRAWT WPDALHIENADSDSWTSNTVKKFTASF EASLSGDRELRTPAVSLKETSGKCPDD HAVRNEAYHRKIISWFGDSPVAVFGLH RLIEFGKKSGKKAGDWYGPAVVAHILR KAVEEARHPDLQGLTIYVAQDCTVYNS DVIDKQTDSVTAGDARDKAVIILVPVRL GGERTNTDYLEFVKGVLSLEYCVGIIGG KPKQSYYFAGFQDDSLIYMDPHYCQSF VDVSIKDFPLETFHCPSPKKMSFRKMDP SCTIGFYCRNVQDFERASEEITKMLKISS KEKYPLFTFVNGHSKDFDFTSTAASEED LFSEDERKNFKRFSTEEFVLL APG4C PREDICTED: XP_001159784.1 MEATGTDEVDKLKTKFISAWNNMKYS 248 APG4 WVLKTKTYFSRNSPVLLLGKCYHFKYE autophagy 4 DEDKTLPAESGCTIEDHVIAGNVEEFRK homolog C DFISRIWLTYREEFPQIEGSALTTDCGW isoform 2 GCTLRTGQMLLAQGLILHFLGRAWTW [Pan PDALNIENSDSESWTSHTVKKFTASFEA troglodytes] SLSGEREFKTPTISLKETIGKYSDDHEM RNEVYHRKIISWFGDSPLALFGLHQLIE YGKKSGKKAGDWYGPAVVAHILRKAV EEARHPDLQGITIYVAQDCTVYNSDVID KQSASMTSDNADDKAVIILVPVRLGGE RTNTDYLEFVKGILSLEYCVGIIGGKPK QSYYFAGFQDDSLIYMDPHYCQSFVDV SIKDFPLETFHCPSPKKMSFRKMDPSCTI GFYCRNVQDFKRASEEITKMLKFSSKE KYPLFTFVNGHSRDYDFTSTTTNEEDLF SEDEKKQLKRFSTEEFVLL APG4C PREDICTED: XP_001250947.1 MEATGTDDVDKLKTKFISAWNNMKYS 249 similar WVLKTKTYFSRNSPVLLLGKCYHFKYE to putative DENELLPARSGCTIEDHVIAGNVEEFRK autophagy- DFISRIWLTYREEFPQIEGSALTTDCGW related GCTLRTGQMLLAQGLILHFLGRAWTW cysteine PDALNIENSDSESWTSNTVKKFTASFEA endopeptidase SLSGERELKTPTISLKEKMERYSDDREM isoform 1 QNEIYHRKIISWFGDSPLALFGLHQLIEC [Bos taurus] GKKSGKKAGDWYGPAVVAHILRKAVE EARHPDLKGITIYVAQDCTVYSSDVIDK QCTSMASDNTNDKAVIILVPVRLGGER TNADYLDFVKGILSLEYCVGIIGGKPKQ SYYFAGFQDDSLIYMDPHYCQSFVDVSI KDFPLETFHCPSPKKMSFRKMDPSCTIG FYCRNVQDFKRASEEITKMLKISSKEKY PLFTFVNGHSRDYDFTSTTTNEEDLFSE DEKKRIKRFSTEEFVLL APG4C PREDICTED: XP_233220.4 MHLNWKCNRPGLLQIPGWVLKTKTYF 250 similar SRNSPVLLLGKCYHFKYEDESKVLPAR to APG4 SGCAIEDHVIAGNVEEFRKDFISRIWLT autophagy 4 YREEFPQIEASALTTDCGWGCTLRTGQ homolog C MLLAQGLILHFLGRAWTWPDALHIESS [Rattus DSDSWTSNTIHKFTASFEASLSGERELR norvegicus] TPAVSLKETSGKHPDDHAVQSEIYHRQI ISWFGDSPVAVFGLHRLIEFGKKSGKKA GDWYGPAVVAHILRKAVEEARHPDLQ GLTIYVAQDCTVYNSDVIDKQTDSVTA GDARDKAVIILVPVRLGGERTNIDYLEF VKGVLSLEYCVGIIGGKPKQSYYFAGF QDDSLIYMDPHYCQSFVDVSIKDFPLET FHCPSPKKMSFRKMDPSCTIGFYCRNV QDFERASEEITKMLKISSKEKYPLFTFV NGHSRDFDFTSTAASEEDLFLEDEKKNF KRFSTEEFVLL APG4C PREDICTED: XP_422520.2 MEATGTDEVEKIKSKFMSAWNNMKYS 251 similar WVLKTKTYFSRNSPVFLLGKCYHFKSD to putative ESGELSTEGSNFDKINTEISGNVEEFRKD autophagy- FISRIWLTYREEFPQIKGSALTTDCGWG related CTLRTGQMLLAQGLMLHFLGRAWVWP cysteine DALDIENSDSESWTAHTVKKLTASLEA endopeptidase SLTAEREPKILSHHQERTLRRDCGDSEM [Gallus RNEVYHRKIISWFGDSPLAAFGLHQLIE gallus] YGKKSGKIAGDWYGPAVVAHILRKAV EEARDPELQGVTVYVAQDCTVYSSDVI DRQCSFMDSGETDTKAVIILVPVRLGGE RTNMDYLEFVKGILSLEYCVGIIGGKPK QSYYFAGFQDDSLIYMDPHYCQSFVDV SIKDFPLESFHCPSPKKMSFKKMDPSCTI GFYCRTVQDFEKASEEITKMLKSSSKEK YPLFTFVKGHSRDYDFASSPLHEENDLF SEDEKKRLKRFSTEEFVLL APG4C PREDICTED: XP_865426.1 MEATGTDEVDKLKTKFISAWNNMKYS 252 similar WVLKTKTYFSRNSPVLLLGKCYHFKFE to APG4 DENKLLPARSGCTIEDHVIAGNVEEFRK autophagy 4 DFISRIWLTYREEFPQIEGSAFTTDCGW homolog C GCTLRTGQMLLAQGLILHFLGRAWTW isoform 4 PDALNIENSDSDSWTSNTVKKFTASFEA [Canis SLSGESELKTPTVSQKETIRRHSDDHEM familiaris] RNEIYHRKIISWFGDSPLALFGLHQLIKY GKKSGKKAGDWYGPAVVAHILRKAVE EARHPDLQGITIYVAQDCTVYSSDVIDK QCTSMASDNTDDKAVIILIPVRLGGERT NTDYLDFVKGILSLEYCVGIIGGKPKQS YYFAGFQDDSLIYMDPHYCQSFVDVSI KDFPLETFHCPSPKKMSFRKMDPSCTIG FYCRNVQDFKRASEEITKMLKISSKEKY PLFTFVNGHSRDYDFTSTTTNEEDLFSE DEKKRLKRFSTEEFVLL APG4D CG6194 NP_650452.1 MNYDGLLSKLTDEKLMLFEAAGEGTIV 253 CG6194-PA EGSRICGQDADPLSLPLVEDGAIEEEQA [Drosophila APIQTIHRTVFAVPRVPSPSPVSTSGANL melanogaster] NLKTENAATATPQRKISTSSRFMNAFSQ LYGGGNSGPSCGHVEQHNEEPGDLSAN RTPTKGMESKLVAMWHNVKYGWSGK MRQTSFSKEQPVWLLGRCYHRRFTPPV SMESSITELPSGADTTPDNATSAFDSIQA TSTSTSLYPALNPQQIDEIVVPQELGMD AVENQVGEQPWEEGIEGFRRDFYSRIW MTYRREFPIMNGSNYTSDCGWGCMLR SGQMLFAQGLICHFLGRSWRYDSESQL HSTYEDNMHKKIVKWFGDSSSKSSPFSI HALVRLGEHLGKKPGDWYGPASVSYL LKHALEHAAQENADFDNISVYVAKDCT IYLQDIEDQCSIPEPAPKPHVPWQQAKR PQAETTKTEQQQHWKSLIVLIPLRLGSD KLNPVYAHCLKLLLSTEHCLGILGGKP KHSLYFVGFQEDRLIHLDPHYCQEMVD VNQENFSLHSFHCKSPRKLKASKMDPS CCIGFYCATKSDFDNFMESVQLYLHPM RCASGATVDKAAGSHHTTPQSSHQTEQ TEMNYPLFSFSRGRCMDHERDEMSDSL YKPLIKQVASLAQELGAQLAPPQHGDE HDQDDSESEEFVLL APG4D APG4-D NP_705811.8 MNSVSPAAAQYRSGSSEDARRADCRRP 254 protein RGQTRIPDPSNLGPSGSGVAALGSSGTD [Mus PAEPDEVDKFKAKFLTAWNNVKYGWA musculus] VKSRTSFSKISTVHLCGRCYHFEGEGDI QRFQRDFVSRLWLTYRRDFPPLAGGSL TSDCGWGCMLRSGQMMLAQGLLLHFL PRDWRWVEGTGLASSEMPGPASPSRCR GPGRRGPPRWTQGALEMEQDRWHRRI VSWFADHPRAPFGLHRLVELGRSSGKK AGDWYGPSVVAHILRKAVESCSEVSRL VVYVSQDCTVYKADVARLLSWPDPTA EWKSVVILVPVRLGGETLNPVYVPCVK ELLRSELCLGIMGGKPRHSLYFIGYQDD FLLYLDPHYCQPTVDVSQPSFPLESFHC TSPRKMAFAKMDPSCTVGFYAGNRKE FETLCSELMRILSSSSVTERYPMFTVAE GHAQDHSLDALCTQLSQPTLRLPCTGR LLKAKRPSSEDFVFL APG4D PREDICTED: XP_512373.2 MQVLHLAGRCPYVSPGWVVKSRTSFS 255 APG4 KISSIHLCGRRYRFEGEGDIQRFQRDFVS autophagy 4 RLWLTYRRDFPPLPGGCLTSDCGWGC homolog D MLRSGQMMLAQGLLLHFLPRDWTWA [Pan EGMGLGPPELSGSASPSRYHGPARWMP troglodytes] PRWAQGAPELEQERRHRQIVSWFADHP RAPFGLHRLVELGQSSGKKAGDWYGP SLVAHILRKAVESCSEVTRLVVYVSQD CTVYKADVARLVARPDPTAEWKSVVIL VPVRLGGETLNPVYVPCVKELLRCELC LGIMGGKPRHSLYFIGYQDDFLLYLDP HYCQPTVDVSQADFPLESFHCTSPRKM AFAKMDPSCTVGFYAGDRKEFETLCSE LTRVLSSSSATERYPMFTLAEGHAQDH SLDDLCSQLAQPTLRLPRTGRLLRAKRP SSEDFVFL APG4D PREDICTED: XP_542069.1 MNSVSPAAAQYRSGSPEDARRPEGRRP 256 similar RGPRVPDPNGPRPSGASGPALGSPAAAP to APG4 GEPDEVDKFKAKFLTAWNNVKYGWA autophagy 4 VKSRTSFSKISSVHLCGRRYRFEGEGDI homolog D QRFQRDFVSRLWLTYRRDFPPLAGGCL isoform 1 TSDCGWGCMLRSGQMMLAQGLLLHFL [Canis PRDWTWAEGPGLGPSEPAGLASPNRYR familiaris] GPARWMPPRWAQGTPELEQERRHRQI VSWFADHPQAPFGLHRLVELGQSSGKK AGDWYGPSLVAHILRKAVESCSEITRLV VYVSQDCTVYKADVARLVARPDPTAE WKSVVILVPVRLGGETLNPVYVPCVKE LLRSELCLGIMGGKPRHSLYFIGYQDDF LLYLDPHYCQPTVDVSQADFPLESFHC TSPRKMAFAKMDPSCTVGFYAGDQKE FETLCSELTRVLSSSSATERYPMFTLAE GHAQDHSLDDLCSQLSQPTLRLPRTGR LLKAKRPSSEDFVFL APG4D AGAP004023- XP_554420.3 AAVRGSDGTKTPGRKISLPPHAHRHES 257 PA VSASCSPMRGGPAANHSTATGGPGEEF [Anopheles KGKVESKLLTMWNNMKFGWSYKMKT gambiae str. NFSKEQPLWLLGRCYHQKITPVTSMES PEST] SVELGTSGPDGQLMVLQNVYFAEPSNS PPEETGTDAIEDSSPEAIVEEEGIDAFRR DFISRIWMTYRREFQTMDDSNYTSDCG WGCMIRSGQMLLAQGLVAHFLGRSWR WDVSMFTAYEESIHRKVIRWFGDTSSK TSPFSIHTLVALGKESGKKPGDWYGPG AVAHLLRQAVRLAAQEITDLDGINVYV AQDCAVYIQDILDECTVPATPAGAPWQ RKGAPGGTNSSSSTAHTERSGATSCAE GDEDVQSAHWKSLILLVPLRLGTDKLN PIYNECLKAMLSLDYCIGIIGGRPKHSL YFVGYQEDKLIHLDPHYCQDMVDVNQ DNFPVASFHCKSPRKMKLSKMDPSCCI GFYCETKKDFYKFIDSVKPFLIPVQPGN QDAGYANPSSGSSTGSVSYPMFVFCRG KSSEQRADLPGQQHQYPHPTAYRSPPT AIPQQAAGGNDDDDEEDEDEAIEFVIL APG4D PREDICTED: XP_873804.1 MNSVSPAAAQYRSGSPEDARRPEGRRP 258 similar RGPRTPDPHGLGPSGASGPALASPGTGP to AUT-like GEPDEVDKFKAKFLTAWNNVKYGWA 4, cysteine VKSRTSFSKISSVHLCGRRYRFEGEGDI endopeptidase QRFQRDFVSRLWLTYRRDFPPLAGGSL isoform 1 TSDCGWGCMLRSGQMMLAQGLLLHFL [Bos taurus] PRDWTWCQGAGLGPSEPPGLGSPSRRR GPARWLPPRWAQAPELEQERRHRQIVS WFADHPRAPFGLHRLVELGQGSGKKA GDWYGPSLVAHILRKAVESCSEVTRLV VYVSQDCTVYKADVARLVARPDPTAE WKSVVILVPVRLGGETLNPVYVPCVKE LLRSELCLGIMGGKPRHSLYFIGYQDDF LLYLDPHYCQPTVDVSQADFPLESFHC TSPRKMAFAKMDPSCTVGFYAGDRKE FETLCSELTRVLSSSSATERYPMFTLVE GHAQDHSLDDLCSPPSQQTLRLPRSGR LLKAKRPSSEDFVFL APG5 APG5 NP_004840.1 MTDDKDVLRDVWFGRIPTCFTLYQDEI 259 autophagy TEREAEPYYLLLPRVSYLTLVTDKVKK 5-like HFQKVMRQEDISEIWFEYEGTPLKWHY [Homo PIGLLFDLLASSSALPWNITVHFKSFPEK sapiens] DLLHCPSKDAIEAHFMSCMKEADALKH KSQVINEMQKKDHKQLWMGLQNDRF DQFWAINRKLMEYPAEENGFRYIPFRIY QTTTERPFIQKLFRPVAADGQLHTLGDL LKEVCPSAIDPEDGEKKNQVMIHGIEPM LETPLQWLSEHLSYPDNFLHISIIPQPTD APG5L APG5 NP_001006409.1 MTDDKDVLRDVWFGRIPTCFTLYQDEI 260 autophagy TEREAEPYYLLLPRISYLTLVTDKVKKH 5-like FQKVMRQEEVNEIWFEYEGTPLKWHY [Gallus PIGLLFDLHASNTALPWSITVHFKNFPE gallus] KDLLHCHSKDVIEAHFMACIKEADALK HKSQVINEMQKKDHKQLWMGLQNDK FEQFWAINRKLMEYPPEDSGFRYIPFRI YQATTERPFIQKLFRPIASGGQLHTLGD LLKDVCPSAITPEDGEKTTQVMIHGIEP MLETPLQWLSEHMSYPDNFLHISIIPRPTD APG5L autophagy NP_001029751.2 MTDDKDVLRDVWFGRIPTCFTLYQDEI 261 protein 5 TEREAEPYYLLLPRVSYLTLVTDKVKK [Bos taurus] HFQKVMRQEDISEIWFEYEGTPLKWHY PIGLLFDLLASSSALPWNITVHFKSFPEK DLLHCPSKDVIEAHFMSCVKEADALKH KSQVINEMQKKDHKQLWMGLQNDRF DQFWAINRKLMEYPAEENGFRYIPFRIY QTTTERPFIQKLFRPVSTDGQLHTLGDL LKEVCPSAVAPEDGEKKNQVMIHGIEP MLETPLQWLSEHLSYPDNFLHISIIPQPTD APG5L autophagy- NP_444299.1 MTDDKDVLRDVWFGRIPTCFTLYQDEI 262 related 5- TEREAEPYYLLLPRVSYLTLVTDKVKK like [Mus HFQKVMRQEDVSEIWFEYEGTPLKWH musculus] YPIGLLFDLLASSSALPWNITVHFKSFPE KDLLHCPSKDAVEAHFMSCMKEADAL KHKSQVINEMQKKDHKQLWMGLQND RFDQFWAINRKLMEYPPEENGFRYIPFR IYQTTTERPFIQKLFRPVAADGQLHTLG DLLREVCPSAVAPEDGEKRSQVMIHGIE PMLETPLQWLSEHLSYPDNFLHISIVPQ PTD APG5L APG5 NP_991181.1 MIMADDKDVLRDVWFGRIPACFTLSPD 263 autophagy ETTEREAEPYYLLLPRVSYLTLVTDKVK 5-like KHFLKVMKAEDVEEMWFEHEGTPLKW protein HYPIGVLFDLHASNSALPWNVTVHFKN isoform 2 FPEQDLLHCSTNSVIEAHFMSCIKEADA [Danio LKHKGQVINDMQKKDHKQLWMGLQN rerio] DKFDQFWAMNRKLMEYPTEEGGFRYI PFRIYQTMSDRPFIQTLFRPVSSEGQALT LGDLLKELFPAAIEDEPKKFQVMIHGIE PLLETPIQWLSEHLSHPDNFLHISIIPAPSD APG5L PREDICTED: XP_001144782.1 MTDDKDVLRDVWFGRIPTCFTLYQDEI 264 hypothetical TEREAEPYYLLLPRVSYLTLVTDKVKK protein HFQKVMRQEDISEIWFEYEGTPLKWHY LOC462905 PIGLLFDLLASSSALPWNITVHFKSFPEK isoform 2 DLLHCPSKDAIEAHFMSCMKEADALKH [Pan KSQVINEMQKKDHKQLWMGLQNDRF troglodytes] DQFWAINRKLMEYPAEENGFRYIPFRIY QTTTERPFIQKLFRPVAADGQLHTLGDL LKEVCPSAIDPEDGEKKNQVMIHGIEPM LETPLQWLSEHLSYPDNFLHISIIPQPTD APG5L PREDICTED: XP_854294.1 MTDDKDVLRDVWFGRIPTCFTLYQDEI 265 similar TEREAEPYYLLLPRVSYLTLVTDKVKK to HFQKVMRQEDISEIWFEYEGTPLKWHY Autophagy PIGLLFDLLASSSALPWNITVHFKSFPEK protein 5- DLLHCPSKDAIEAHFMSCVKEADALKH like (APG5- KSQVINEMQKKDHKQLWMGLQNDRF like) DQFWAINRKLMEYPAEENGFRYIPFRIY (Apoptosis- QTTTERPFIQKLFRPVAADGQLHTLGDL specific LKEVCPSAIAPEDGEKKNQVMIHGIEPM protein) LETPLQWLSEHLSYPDNFLHISIIPQPTD isoform 1 [Canis familiaris] APG7 ATG7 NP_001012097.1 MGDPGLSKLQFAPFNSALDVGFWHELT 266 autophagy QKKLNEYRLDEAPKDIKGYYYNGDSA related 7 GLPTRLTLEFSAFDMSAPTPARCCPAM homolog GTLHNTNTLEAFKTADKKLLLEQSANEI [Rattus WEAIKSGAALENPMLLNKFLLLTFADL norvegicus] KKYHFYYWFCCPALCLPESIPLIRGPVG LDQRLSPKQIQALEHAYDDLCRTEGVT ALPYFLFKYDDDTVLVSLLKHYSDFFQ GQRTKLTVGVYDPCNLTQHPGWPLRN FLVLAAHRWSGSFQSVEVLCFRDRTMQ GARDVTHSIIFEVKLPEMAFSPDCPKAV GWEKNQKGGMGPRMVNLSGCMDPKR LAESSVDLNLKLMCWRLVPTLDLDKV VSVKCLLLGAGTLGCNVARTLMGWGV RHVTFVDNAKISYSNPVRQPLYEFEDCL GGGKPKALAAAERLQKIFPGVNASGFN MSIPMPGHPVNFSDVTMEQARRDVEQL EELIDSHDVIFLLMDTRESRWLPTVIAA SKRKLVINAALGFDTFVVMRHGLKKPK QQGAGDLCPSHLVAPADLGSSLFANIP GYKLGCYFCNDVVAPGDSTRDRTLDQ QCTVSRPGLAVIAGALAVELMVSVLQH PEGGYAIASSSDDRMNEPPTSLGLVPHQ IRGFLSRFDNVLPVSLAFDKCTACSSKV LDQYEQEGFTFLAKVFNSSHSFLEDLTG LTLLHQETQAAEIWDMSDEETV APG7 APG7 NP_006386.1 MAAATGDPGLSKLQFAPFSSALDVGFW 267 autophagy HELTQKKLNEYRLDEAPKDIKGYYYNG 7-like DSAGLPARLTLEFSAFDMSAPTPARCCP [Homo AIGTLYNTNTLESFKTADKKLLLEQAA sapiens] NEIWESIKSGTALENPVLLNKFLLLTFA DLKKYHFYYWFCYPALCLPESLPLIQGP VGLDQRFSLKQIEALECAYDNLCQTEG VTALPYFLIKYDENMVLVSLLKHYSDF FQGQRTKITIGVYDPCNLAQYPGWPLR NFLVLAAHRWSSSFQSVEVVCFRDRTM QGARDVAHSIIFEVKLPEMAFSPDCPKA VGWEKNQKGGMGPRMVNLSECMDPK RLAESSVDLNLKLMCWRLVPTLDLDK VVSVKCLLLGAGTLGCNVARTLMGWG VRHITFVDNAKISYSNPVRQPLYEFEDC LGGGKPKALAAADRLQKIFPGVNARGF NMSIPMPGHPVNFSSVTLEQARRDVEQ LEQLIESHDVVFLLMDTRESRWLPAVIA ASKRKLVINAALGFDTFVVMRHGLKKP KQQGAGDLCPNHPVASADLLGSSLFAN IPGYKLGCYFCNDVVAPGDSTRDRTLD QQCTVSRPGLAVIAGALAVELMVSVLQ HPEGGYAIASSSDDRMNEPPTSLGLVPH QIRGFLSRFDNVLPVSLAFDKCTACSSK VLDQYEREGFNFLAKVFNSSHSFLEDLT GLTLLHQETQAAEIWDMSDDETI APG7L APG7 NP_001025763.1 MAAVSNESQNPVDPGSSKLQFAPFSSA 268 autophagy LNVGFWHELTQKKLNEYRLDETPKVIK 7-like GYYYNGDPSGFPARLTLEYSAFDINASI [Gallus PARCCPAFGTLYNTNTFETFKSCDKKSL gallus] LEKEANEIWESIKSGAALENPMLLNRFL LLTFADLKKYHFYYWFCYPALCFPDGI HVIQKPVCLGDRFSLNQIQALQKAYDE LCQTEGVTAFPYFLIKYHDNSVVVSPLK KWDGFFQDQGGKVTVGVYDPCNLSHY PGWPLRNFLILASHKWGNILQSIEVLCF RDRTMQGVRDITHSIIFEIKLPQGAFGPD CPKAVGWEKNQKGGMGPRVVNLSEC MDPKRLAESSVDLNLKLMCWRLVPTL DLEKIVSAKCLLLGAGTLGCSVARTLM GWGVRKITFVDNARISYSNPVRQPLYE FEDCLSGGKPKALAAAERLQKIFPGVN SEGYNMSIPMPGHPVNFSEVTMAQARK DVATLEELIDAHDVVFLLMDTRESRWL PAVIAASKRKLVINAALGFDTFVVMRH GLKKPKQQETGNACFSTAPGPSDLLGS SLFSNIPGYKLGCYFCNDVVAPGDSTR DRTLDQQCTVSRPGLAMIAGALAVELM VSVLQHPEGGYAVASSSDDRMNEPPTS LGLVPHQIRGFLSRFDNVLPVSLAFDKC TACSPKVLDQYEREGFNFLAKVFNSSH SFLEDLTGLTLLHQETQAAEIWDMSDD ETV APG7L AuTophaGy NP_502064.1 MATFVPFVTCLDTGFWNEVNKKKLND 269 (yeast Atg WKLDETPKCISSQLSLHQTEGFKCHLSL homolog) SYDSLSSLESTTGLSMSGTLLLYNTIESF family KMVDKSDLIRSEAEKIWESITTRKWLQ member NPRLLSQFFIIAFADLKKFKYYYWTCVP (atg-7) ALVYPSEIKQEITPLSSLGADHKILFDFY [Caenorhabditis RKNNFPIFLYSKQSSKMLELSELENNTN elegans] PDEICVVVADPSPVAYSAGWMVRNVL AAVAHLHPTWKHCHIISLRSADSIGIKY TWTLPSAECSADGAQNAVPKAVGWER NANDKLQPISVDLSKEFDPKILMERSVD LNLSLIKWRLHPDIQLERYSQLKVLILG AGTLGCNIARCLIGWGVRHISFLDNSTV SYNNPVRQSLSEFEDARLGRGKAETAQ AAIQRIFPSIQATAHRLTVPMPGHSIDEK DVPELEKDIAKLEQLVKDHDVVFLALD SREARWLPTVLASRHKKIAISVAIGFDT YVIIRHGIGSRSESVSDVSSSDSVPYSQL SCYFCSDVTAPGNSTFDRTLDQQCTVA RPGTSMIASGIAVELLSSVLQYPDPLKT PASHDDNTTVLGAAPHQIRGFLGRFQQI LPSVKRFDQCVACGDAIAAQFQQNGW KFVRDVMNSPGRLEEVTGLDELQNSVN AIDIDFEDDEDF APG7L unnamed XP_451226.1 MLNDLKFSPAFKSFVDTSFFHELSRLKL 270 protein EVFKLDSAEKELFSALDLENITSNTVSL product SLRDDSFDPVLNNEAVTLKGSVLNFNTI [Kluyveromyces ESFKSCDKVKFIKEKGQQLLEQGLKNG lactis] LKECVRFYVISFADLKKYKFYYWVCM PTFQSEGSSYEIISTKSIEDGVKKDIWEQ NSFISCVVDGKIQEASPQYLKVCQKVIF KDFSRLKGIPAAVTKNFLTVWSQISTRN TYTICFLRDDNSSFAAEIRVTGSNTGCL KVSGWEKNGLGKLAPKSADLSSLMDP VKIAEQSIDLNLKLMKWRIAPDIDLERI KNIKALILGSGTLGCYVARALLAWGTR HVTFVDNSTVSFSNPVRQPLFNFEDCGR PKAEAASDSLKKIFPSVVSAGYQLEIPM IGHPVSNESKQRKDYEILDELIRTHDVIF LLMDARETRWLPSVLGRMHEKIVINAA LGFDSYLVMRHGNNNDNLGCYFCNDI VAPSDSLTDRTLDQMCTVTRPGVALLA ASQAVELLVTYLQPSTNVLGSAPHQIR GFLNEFKTVKLETPAYQHCCASNENVIL TLKENGWNFVKQALDDYKCVEQLSGL SKVQEEAELAIQEDISFDDDEELSIE APG7L PREDICTED: XP_849849.1 MAAALGDPGLSKLLFAPFSSALDVGFW 271 similar HELTQRKLNEYRLDEAPKDIKGYYYNG to APG7 DSAGLPARLTLEFSAFDMSAPTPAHCCP autophagy AVGTLFNTNTLEAFKAADKKLLLEQAA 7-like DEIWEAIKSGAALENPVLLNKFLLLTFA isoform 3 DLKKYHFYYWFCFPALCLPESIPLIQGP [Canis VGLDQRFSPKQIQALEHAYDDLCQTEG familiaris] VPALPYFLIKYDENMVLVSLLKHYSDF FQDQRTKITIGVYDPCNLAQHPGWPLR NLLVLAAHRWSSCFQSVEVLCFRDRTM QGMRDIAHSIIFEVKLPEMAFSPDCPKA VGWEKNQKGGMGPRMVNLSECMDPK RLAESSVDLNLKLMCWRLVPTLDLEKV VSVKCLLLGAGTLGCNVARTLMGWGV RHITFVDNANISYSNPVRQPLYEFEDCL AGGKPKALAAADRLQKIFPGVNARGFN MSIPMPGHPVNFSSVTLDQARRDVEQL EQLIESHDVVFLLMDTRESRWLPAVIAA SKRKLVINAALGFDTFVVMRHGLKKPK QQGAGDLCSGHLVAPADLLGSSLFANI PGYKLGCYFCNDVVAPGDSTRDRTLD QQCTVSRPGLAMIAGALAVELMVSVL QHPEGGYAIASSSDDRMNEPPTSLGLVP HQIRGFLSRFDNVLPVSLAFDKCTACSS KVLDQYEREGFNFLAKVFNSSHSFLED LTGLTLLHQETQAAEIWDMSDDETV APG8 microtubule- NP_073729.1 MPSEKTFKQRRTFEQRVEDVRLIREQHP 272 associated TKIPVIIERYKGEKQLPVLDKTKFLVPD proteins HVNMSELIKIIRRRLQLNANQAFFLLVN 1A/1B light GHSMVSVSTPISEVYESEKDEDGFLYM chain 3 VYASQETFGMKLSV [Homo sapiens] APG8a microtubule- NP_001039640.1 MPSDRPFKQRRSFADRCKEVQQIREQH 273 associated PSKIPVIIERYKGEKQLPVLDKTKFLVPD protein 1 HVNMSELVKIIRRRLQLNPTQAFFLLVN light chain 3 QHSMVSVSTPIADIYEQEKDEDGFLYM alpha [Bos VYASQETFGF taurus] APG8a microtubule- NP_080011.1 MPSDRPFKQRRSFADRCKEVQQIRDQH 274 associated PSKIPVIIERYKGEKQLPVLDKTKFLVPD protein 1 HVNMSELVKIIRRRLQLNPTQAFFLLVN light chain 3 QHSMVSVSTPIADIYEQEKDEDGFLYM alpha [Mus VYASQETFGF musculus] APG8a microtubule- NP_955794.1 MPSDRPFKQRRSFADRCKEVQQIRDQH 275 associated PSKIPVIIERYKGEKQLPVLDKTKFLVPD protein 1 HVNMSELVKIIRRRLQLNPTQAFFLLVN light chain 3 QHSMVSVSTPIADIYEQEKDEDGFLYM alpha VYASQETFGF [Rattus norvegicus] APG8a microtubule- NP_999904.1 MPSDRPFKQRRSFADRCKEVQQIREQH 276 associated PNKIPVIIERYKGEKQLPVLDKTKFLVP protein 1 DHVNMSELVKIIRRRLQLNPTQAFFLLV light chain 3 NQHSMVSVSTPISEIYEQERDEDGFLYM alpha VYASQETFGC [Danio rerio] APG8a PREDICTED: XP_001159668.1 MPSDRTFQQRRSFSDRCKEVQQIRDQH 277 microtubule- PSKIPVIIERYKGEKQLPVLDKTKFLVPD associated HVNMSELVKIIRRRLQLNPTQAFFLLVN protein 1 QHSMVSVSTPIADIYEQEKDEDGFLYM light chain 3 VYASQETFGF alpha isoform 2 [Pan troglodytes] APG8b microtubule- NP_001026632.1 MPSEKSFKQRRTFEQRVEDVRLIRDQH 278 associated PTKIPVIIERYKGEKQLPVLDKTKFLVPD proteins HVNMSELIKIIRRRLQLNSNQAFFLLVN 1A/1B light GHSMVSVSTPISEVYESEKDEDGFLYM chain 3 VYASQETFGVQSSV [Gallus gallus] APG8b microtubule- NP_074058.2 MPSEKTFKQRRSFEQRVEDVRLIREQHP 279 associated TKIPVIIERYKGEKQLPVLDKTKFLVPD protein 1 HVNMSELIKIIRRRLQLNANQAFFLLVN light chain 3 GHSMVSVSTPISEVYESERDEDGFLYM beta [Rattus VYASQETFGTALAV norvegicus] APG8b microtubule- NP_080436.1 MPSEKTFKQRRSFEQRVEDVRLIREQHP 280 associated TKIPVIIERYKGEKQLPVLDKTKFLVPD protein 1 HVNMSELIKIIRRRLQLNANQAFFLLVN light chain 3 GHSMVSVSTPISEVYESERDEDGFLYM beta [Mus VYASQETFGTAMAV musculus] APG8b microtubule- NP_955898.1 MPSEKTFKQRRTFEQRVEDVRLIREQHP 281 associated NKIPVIIERYKGEKQLPILDKTKFLVPDH protein 1 VNMSELIKIIRRRLQLNSNQAFFLLVNG light chain 3 HSMVSVSTAISEVYERERDEDGFLYMV beta [Danio YASQETFGFQ rerio] APG8b PREDICTED: XP_001150056.1 MSSGLRAADFPRWKRHISEQLRRRDRL 282 APG16 QRQAFEEIILQYNKLLEKSDLHSVLAQK autophagy LQAEKHDVPNRHEISPGHDGTWNDNQ 16-like LQEMAQLRIKHQEELTELHKKRGELAQ isoform 9 LVIDLNNQMQRKDREMQMNEAKIAEC [Pan LQTISDLETECLDLRTKLCDLERANQTL troglodytes] KDEYDALQITFTALEGKLRKTTEENQEL VTRWMAEKAQEANRLNAENEKDSRRR QARLQKELAEAAKEPLPVEQDDDIEVIV DETSDHTEETSPVRAISRAATRRSVSSFP VPQDNVDTHPGSGKEVRVPTTALCVFD AHDGEVNAVQFSPGSRLLATGGMDRR VKLWEVFGEKCEFKGSLSGSNAGITSIE FDSAGSYLLAASNDFASRIWTVDDYRL RHTLTGHSGKVLSAKFLLDNARIVSGS HDRTLKLWDLRSKVCIKTVFAGSSCND IVCTEQCVMSGHFDKKIRFWDIRSESIV REMELLGKITALDLNPERTELLSCSRDD LLKVIDLRTNAIKQTFSAPGFKCGSDWT RVVFSPDGSYVAAGSAEGSLYIWSVLT GKVEKVLSKQHSSSINAVAWSPSGSHV VSVDKGCKAVLWAQY APG8b PREDICTED: XP_536756.2 MPSEKTFKQRRTFEQRVEDVRLIREQHP 283 similar TKIPVIIERYKGEKQLPVLDKTKFLVPD to HVNMSELIKIIRRRLQLNANQAFFLLVN microtubule- GHSMVSVSTPISEVYESEKDEDGFLYM associated VYASQETFGMKLFV proteins 1A/1B light chain 3 [Canis familiaris] APG8c PREDICTED: XP_514305.2 MPPPQKIPSVRPFKQRKSLAIRQEEVAGI 284 microtubule- RAKFPNKIPVIVERYPRETFLPLLDKTKF associated LVPQELTMTQFLSIIRSRMVLRATEAFY protein 1 LLVNNKSLVSMSATMAEIYRDYKDED light chain 3 GFVYMTYASQETFGCLESAAPRDGSSL gamma [Pan EDRPCNPL troglodytes] APG8c PREDICTED: XP_854448.1 MQTPQKTQSLRPFKQRKSLATRQEEVA 285 similar GIRAKFPNKIPVIVERYPREKFLPLLDKT to KFLVPQELTMIQFLSIIRSRLVLGATEAF microtubule- YLLVNNRSLVSMSMTMAEVYRDYKDE associated DGFVYMTYASQEMFGCLGSEQILPSSP protein 1 VHVKNQCSNLRRDGSSPVCVVDNPVSE light chain 3 AAPQ gamma [Canis familiaris] APG9 APG9 NP_001070666.1 MAQFDTEYQRLEASYSDSPPGEEDLLV 286 autophagy HVAEGSKSPWHHIENLDLFFSRVYNLH 9-like 1 QKNGFTCMLIGEIFELMQFLFVVAFTTF [Homo LVSCVDYDILFANKMVNHSLHPTEPVK sapiens] VTLPDAFLPAQVCSARIQENGSLITILVI AGVFWIHRLIKFIYNICCYWEIHSFYLH ALRIPMSALPYCTWQEVQARIVQTQKE HQICIHKRELTELDIYHRILRFQNYMVA LVNKSLLPLRFRLPGLGEAVFFTRGLKY NFELILFWGPGSLFLNEWSLKAEYKRG GQRLELAQRLSNRILWIGIANFLLCPLIL IWQILYAFFSYAEVLKREPGALGARCW SLYGRCYLRHFNELEHELQSRLNRGYK PASKYMNCFLSPLLTLLAKNGAFFAGSI LAVLIALTIYDEDVLAVEHVLTTVTLLG VTVTVCRSFIPDQHMVFCPEQLLRVILA HIHYMPDHWQGNAHRSQTRDEFAQLF QYKAVFILEELLSPIVTPLILIFCLRPRAL EIIDFFRNFTVEVVGVGDTCSFAQMDV RQHGHPQWLSAGQTEASVYQQAEDGK TELSLMHFAITNPGWQPPRESTAFLGFL KEQVQRDGAAASLAQGGLLPENALFTS IQSLQSESEPLSLIANVVAGSSCRGPPLP RDLQGSRHRAEVASALRSFSPLQPGQA PTGRAHSTMTGSGVDARTASSGSSVWE GQLQSLVLSEYASTEMSLHALYMHQLH KQQAQAEPERHVWHRRESDESGESAP DEGGEGARAPQSIPRSASYPCAAPRPGA PETTALHGGFQRRYGGITDPGTVPRVPS HFSRLPLGGWAEDGQSASRHPEPVPEE GSEDELPPQVHKV APG9L autophagy- NP_001003917.2 MAQFDTEYQRLEASYSDSPPGEEDLLV 287 related 9- HVAEGSKSPWHHIENLDLFFSRVYNLH like 1 [Mus QKNGFTCMLIGEMFELMQFLFVVAFTT musculus] FLVSCVDYDILFANKMVNHSLHPTEPV KVTLPDAFLPAQVCSARIQENGSLITILV IAGVFWIHRLIKFIYNICCYWEIHSFYLH ALRIPMSALPYCTWQEVQARIVQTQKE HQICIHKRELTELDIYHRILRFQNYMVA LVNKSLLPLRFRLPGLGEVVFFTRGLKY NFELILFWGPGSLFLNEWSLKAEYKRG GQRLELAQRLSNRILWIGIANFLLCPLIL IWQILYAFFSYAEVLKREPGALGARCW SLYGRCYLRHFNELEHELQSRLNRGYK PASKYMNCFLSPLLTLLAKNGAFFAGSI LAVLIALTIYDEDVLAVEHVLTTVTLLG VTVTVCRSFIPDQHMVFCPEQLLRVILA HIHYMPDHWQGNAHRSQTRDEFAQLF QYKAVFILEELLSPIVTPLILIFCLRPRAL EIIDFFRNFTVEVVGVGDTCSFAQMDV RQHGHPQWLSGGQTEASVYQQAEDGK TELSLMHFAITNPGWQPPRESTAFLGFL KEQVQRDGAAAGLAQGGLLPENALFTS IQSLQSESEPLSLIANVVAGSSCRGPSLS RDLQGSRHRADVASALRSFSPLQPGAA PQGRVPSTMTGSGVDARTASSGSSVWE GQLQSLVLSEYASTEMSLHALYMHQLH KQQTQAEPERHVWHRRESDESGESAPE EGGEGARAPQPIPRSASYPCATPRPGAP ETTALHGGFQRRYGGITDPGTVPRGPS HFSRLPLGGWAEDGQPASRHPEPVPEE GSEDELPPQVHKV APG9L autophagy- NP_001014240.1 MAQFDTEYQRLEASYSDSPPGEEDLLV 288 related 9A HVAEGSKSPWHHIENLDLFFSRVYNLH [Rattus QKNGFTCMLIGEIFELMQFLFVVAFTTF norvegicus] LVSCVDYDILFANKMVNHSLHPTEPVK VTLPDAFLPAQVCSARIQENGSLITILVI AGVFWIHRLIKFIYNICCYWEIHSFYLH ALRIPMSALPYCTWQEVQARIVQTQKE HQICIHKRELTELDIYHRILRFQNYMVA LVNKSLLPLRFRLPGLGEVVFFTRGLKY NFELILFWGPGSLFLNEWSLKAEYKRG GQRLELAQRLSNRILWIGIANFLLCPLIL IWQILYAFFSYAEVLKREPGALGARCW SLYGRCYLRHFNELEHELQSRLNRGYK PASKYMNCFLSPLLTLLAKNGAFFAGSI LAVLIALTIYDEDVLAVEHVLTTVTLLG VTVTVCRSFIPDQHMVFCPEQLLRVILA HIHYMPDHWQGNAHRSQTRDEFAQLF QYKAVFILEELLSPIVTPLILIFCLRPRAL EIIDFFRNFTVEVVGVGDTCSFAQMDV RQHGHPQWLSGGQTEASVYQQAEDGK TELSLMHFAITNPGWQPPRESTAFLGFL KEQVQRDGAAAGLAQGGLLPENALFTS IQSLQSESEPLSLIANVVAGSSCRGPPLS RDLQGSRHRADVASALRSFSPLQPGQA PQGRVPSTMTGSGVDARTASSGSSVWE GQLQSLVLSEYASTEMSLHALYMHQLH KQQTQAEPERHVWHRRESDESGESAPE EGGEGARAPQPIPRSASYPCATPRPGAP ETTALHGGFQRRYGGITDPGTVPRAPS HFSRLPLGGWAEDGQPASRHPEPVPEE GSEDELPPQVHKV APG9L ATG9 NP_001029878.1 MAQFDTEYQRLEASYSDSPPGEEDLLV 289 autophagy HVPEGSKSPWHHIENLDLFFSRVYNLH related 9 QKNGFTCMLIGEIFELMQFLFVVAFTTF homolog A LVSCVDYDILFANKMVNHSLHPTEPVK [Bos taurus] VTLPDAFLPAQVCSARIQENGSLITILVI AGVFWVHRLIKFIYNICCYWEIHSFYLH ALRIPMSALPYCTWQEVQARIVQTQKE HQICIHKRELTELDIYHRILRFQNYMVA LVNKSLLPLRFRLPGLGEVVFFTRGLKY NFELILFWGPGSLFLNEWSLKAEYKRG GQRLELAQRLSNRILWIGIANFLLCPLIL IWQILYAFFSYAEVLKREPGALGARCW SLYGRCYLRHFNELEHELQSRLNRGYK PASKYMNCFLSPLLTLLAKNCAFFAGSI LAVLIALTIYDEDVLAVEHVLTTVTLLG VTVTVCRSFIPDQHMVFCPEQLLRVILA HIHYMPDHWQGNAHRSQTRDEFAQLF QYKAVFILEELLSPIVTPLILIFCLRPRAL EIIDFFRNFTVEVVGVGDTCSFAQMDV RQHGHPQWLSGGQTEASVYQQAEDGK TELSLMHFAITNPGWQPPRESTAFLGFL KEQVQRDGAAAGLAQGGLLPENALFTS IQSLQSESEPLSLIANVVAGSSCRGPPLP RDLQGSRHRAEVASALRSFSPLQPGQA PTGRAPSTMTGSGVDARTASSGSSVWE GQLQSLVLSEYASTEMSLHALYMHQLH KQQAQAEPERHVWHRRESDESGESAPE EGGEGARATQPIPRSASYPCAAPRPGAP ETTALQGGFQRRYGGITDPGTVPRAPS HFSRLPLGGWAEDGQSASRHPEPVPEE GSEDELPPQVHKV APG9L ATG9 NP_001029993.1 MAHLETQYQRLESSSTESPPGGGDLLV 290 autophagy HVPEGAKSPWHHIENLDLFFSRVYNLH related 9 QKNGFTCMLIGEIFELMQFIFVVAFTTF homolog A LISCVDYDILFANKAVNHSQHPSEPIKV [Gallus TLPDAFLPPNVCSARIQANSFLICILVIA gallus] GVFWIHRLVKFIYNICCYWEIHSFYINA LRIPMSNLPYYTWQEVQARIVQIQKEH QICIHKKELTELDIYHRILRFKNYMVAM VNKSLLPIRFRLPLLGDTVFYTRGLKYN FELIFFWGPGSLFENEWSLKAEYKRAG NRLELAEKISTRILWIGIANFLLCPLILIW QILYAFFSYTEILKREPGSLGARCWSLY GRCYLRHFNELDHELQSRLSKGYKPAS KYMNCFISPLLTIVAKNVAFFAGSILAV LIALTIYDEDVLAVEHVLTTVTLLGVGI TVCRSFIPDQHLVFCPEQLLRVILAHIHY MPDHWQGNAHRYETRDEFAQLFQYKA VFILEELLSPIITPLILIICLRPKSLDIVDFF RNFTVEVVGVGDTCSFAQMDVRQHGH PAWMSAGKTEASIYQQAEDGKTELSL MHFAITNPKWQPPRESTAFIGFLKERVH RDSSVALAQQAVLPENALFSSIQSLQSE SEPHSLIANVIAGSSVLGFHMGRDGQAS RHLSEVASALRSFSPLQSAQQPSAGFQT GGSSAMTASGADARTMSSGSSAWEGQ LQSMILSEYASTEMSLHALYMHELHKQ HAQLEPERHTWHRRESDESGESTHEEL DAQRGAPVPLPRSASYPFSSRQPAEETA TLQTGFQRRYGGITDPGTVHRAPSHFSR LPLGGWAEDGQSARHPEPVPEESSEDE LPPQIHKV APG9L Os01g0200000 NP_001042313.1 MQVKQKVYELYKGTVERVTGPRTVSA 291 [Oryza FLDKGVLSVPEFILAGDNLVSKCPTWS sativa WEAGDPSKRKPYLPPDKQFLVTRNVPC (japonica LRRAVSLEEEYDAAGAEVVLGDDEDG cultivar- EGWLATHGVQASKQEEEEDIPSMDTLD group)] IGKTEGIKSIPSYFSAGKKAEEEEDIPDM DTYEDSGNDSVATAQPSYFVAEEPEDD NILRTRTYDVSITYDKYYQTPRVWLTG YDESRMPLKPELVFEDISQDHARKTVTI EDHPHLSAGKHASVHPCKHAAVMKKII DVLMSQGVEPEVDKYLFIFLKFMASVIP TIEYDYTMDFDLGSTSR APG9L Os01g0614900 NP_001043569.1 MAARAEAAAAAPRPLQAAAIGVCAET 292 [Oryza GFWDALRRLKLDVLGTDDSPIPITGYYT sativa PRQYEKIASLFRICPESILPPSANSFGDR (japonica NNCPVPGTLLNTNNMRGFQNLDRALLL cultivar- KAEAKKILHDIKSGKVEENPALLLRFLV group)] ISFADLKNWKVYYNVAFPSLIFDSKITL LSLKLASQVLKQEEATSLSNAFTEWRK SSETTVVPFFLINISPDSSATIRQLKDWK ACQGNGQKLLFGFYDHGNRGFPGWAL RNYIAFVSLRWKIEKVHFFCYREKRGR PDIQQSLVGEASFPAPHAGWDEPDYVP EAIGWEGETAGKESKEMKPKEIDLSSIN PASQDEEKQLMHLKLMGWRHFPVNLD KLAGVRCLLLGAGTLGCEVARLLMTW GVRKLTVVDDGCVSMSDLVKQSLYTD KDCGVPRVTAIVPHLKERCSAVEVEGI QMGIPKLEYNISASKISSITDDCKRLQTL VDSNDVVFLLNETWEGMWLPTLLCAD KNKIAITVLLGYDNYLVMRHGAGPGTK SGGMDEGIAQIENLSTQDALGRQRLGC CFCSDTTSLVNSDHNGALDQQSAVILP GLTSVASGKAVELFARMLHHPDEIHAP GDIAGTDTEHQLGLLPHQMQGSLSKCV LSTVLCNSSSNCIACSNAVLSEYRRRGF DFVTQAITCPTYLKDLTGISDLKKPFAS KISASIPVSKTSASIPVNLEKLSSARCLLL GAGTLGCDVARILMDCGVRKLTVVDS GRVVVSNLARQSLYTSDDRDSPKASAI LGRLKERCPSVDAKGIKMEIPMPGHPV SPNEAVSVLEDCKRLQELVSSHDAVFL LTDTRESRWLPTLLCANENKIAITAALG YDSYLVMRHGAGPGTNCGSPDVVAAA DTLSAEDVLGRQRLGCYFCNDVVAPV DSVSNRTLDQQCTVTRPGLSSITSGCAA DLFTRMLHHPDGIHAPGEIAGTSSEGPL GLLPHQIRGSLSQYNLLTLLGYSSSNCT ACSNAVLSEYHRRGMDFVMQVINEPT YLEDLTGLTDLMKSAAYSQVEWIDEVD DDDEMDI APG9L Os01g0681400 NP_001043880.1 MKAPAAAAAAVGNRAGGVDPSIPRFK 293 [Oryza CQECHRALVVVGVDSFADKLPAQATS sativa AHASSVHGSIMGASRMDNSYVVLSKQ (japonica NKSHGHGIPPRPPSAAAPHIEPNQPTRA cultivar- MEGSYIVLPPAAASIYKTSTSEGGGAQL group)] PPPSINSSSLLPGNSFHSNVTVLKRAFEI ATSQTQVEQPMCLDCMRLLSDKMDKE IEDVNADIKAYEVCLQHLEQESHTVLSD AGFQKEKLKIEEEEKKLNAAIEEAEKQY SEISSEMKDLEIKSKEFEELEERYWHEF NSFQFQLTSHQEERDAILAKIEVSQVHL ELLKQTNVLNDAFYISHDGVIGTINNFR LGRLPNVQVEWDEINAAWGQAALLLH TMAQYFTPKFEYRIKIHPMGSYPRVTDI HKNTYELFGPVNLFWSTRFDKAMTWF LTCLQDFAEFAISLDKENNVPPEKSLKL PYKIDGDKVGSHTIFLSFNKVENWTKA LKYTLCNLKWVLYWFIGNTSFAPPSGS LCAAQSSKR APG9L Os02g0117800 NP_001045690.1 MAAQRDDEAGWSAEAARRVWGGAVP 294 [Oryza LQVHLHDADVTTLPPPPPFLTLGPRIGY sativa LPLLVPIIKAHFSSTLPPGIDTVWFEYKG (japonica LPLKWYIPIGVLYDLLCADPERPWNLT cultivar- VHFRGYPSEILTLCDGEDSVKWSYMNS group)] LKEAAFIITGNSKNVMNMSQADQGAL WQSVMKGNLDGYMNISTRLKLGPFEE DCLVRTSSVEGQQGSDEPESPGSGKPCR VPVRLYVRSVQEDLYDLEDALPVGDW ESISYINRPFEVRREEGRSYITLEHALKT LLPEFFSSKASRIPDDSETAPQAPDSAPN DDSDVTPRSCEKLESSASSSPQEANVAN KGKIVKLVRVQGIEVDMDIPFLWVANN LKNPECYLHICVYVGTRKREPKDGR APG9L Os03g0248000 NP_001049553.1 MMSFRSKDRNVQPRFNWPWRSESPLS 295 [Oryza AQLLIDIPPEIELSDYRRLPGSGSESPSGL sativa LHGEGFKDEPIADLDIFFERLYEYFCAK (japonica GLRCIVTKWIIEMLNVLFMVCCIGFFFLI cultivar- VDWNALGHLKCGVEALESGEKPCDLM group)] QVVKHNPLVPFTFPKMITIGSMVILTTY GLINFLKFFVQLRSTLNIRDFYCNSLKIT DLEIQTISWPKIIEKVVLLQKSQKLCVV RDLSEHDIIMRIMRKENYLIGMVNKGIIS FPIRPWVPGAGPTVKSHLQNRRNHLILP KALEWTLNWCIFQSMFDSKFCVRKDFL TSPAVLKKRLVFVGISMLILSPCLVIFPL VYLILRHAEEIYNHPSTASSRRWSNLSR WIFREYNEVDHFFRHRMNNSAVHSLN YLKQFPTPLISIMAKFISFVSGGLAGALII IGFLGESVLEGHIFGRNLFWYTIVFGTIA AISRKVVADELQVIDPEGAMCNVVQQT HYMPKRWRGKEDSEVVRREFETLFQFT IVMLLEEMASIFISPYLLIFEVPKRVDDIL RFISDFTIYVDGVGDVCSLSLFDFRRHG NRNYASPFDALKTLRSSQGKMEKSFLS FQSVYPSWEPNAEGKQFLTNLQKFKEK QIRQQALAQYQAMEASGFVASTRGHR DDIFHQLLPSDIHNRAEAISPAVYNLGP LGLLDTDQRSHPYILDWYYVCHPPHLD RTEAPYFNEVFPETSENTGSAAFKASEI EEARGWDSDMVPPPRADRDEWNFNHE RVRSHMDASTSSNLFHHAPVEHHDTKG NIIDWWDQAPEHSTGQQGSFLEPPEFG NRYVAGNRSSYHSGDVSDGSVEELERS YNRSSSSWRRPQDLSTTRYMDDSDIEE GLNLPFADLPQKDEDARHGTSDTNDPT PVGLPVRIIPRSSDPV APG9L Os03g0391000 NP_001050279.1 MKEDESPPHPHRSIPFHPSPPRDGSDSG 296 [Oryza GSVAAVPPSPRAAAAAAARPPVMTSLP sativa GRGVSPSSSDPLCEGNAAPSSSSSSGQD (japonica LKQLKNSILSCVFSSPFSIFEAHQDSSAN cultivar- RSLKPHSGSYAWSRFLRRIACTGSMWR group)] FLGASKALTSSDVWFLGKCYKLSSEEL SNSSDCESGNAAFLEDFSSRIWITYRKG FDAISDSKYTSDVNWGCMVRSSQMLV AQALIFHHLGRSWRKPSQKPYSPEYIGI LHMFGDSEACAFSIHNLLQAGKSYGLA AGSWVGPYAMCRAWQTLVCTNREHH EAVDGNGNFPMALYVVSGDEDGERGG APVVCIDVAAQLCCDFNKNQSTWSPIL LLVPLVLGLDKLNPRYIPLLKETLTFPQS LGILGGKPGTSTYIAGVQDDRALYLDP HEVQLAVDIAADNLEAGTSSYHCSTVR DLALDLIDPSLAIGFYCRDKDDFDDFCS RASELVDKANGAPLFTVVQSVQPSKQ MYNEESSSGDGMDSINVEGLDGSGETG EEEWQIL APG9L Os03g0746600 NP_001051251.1 MTMVEAEAGKEAIRRALRSLRRRHLVE 297 [Oryza EGAHRPAIEALARPFAAQAVEWKEKAE sativa KHELELQQCYKAQSRLSEQLVTEIEEGK (japonica ASKALLKEKETLITTMQTELEQTREENT cultivar- QLKQSLEEKTSALDLIIQEHQAVKAELE group)] QALTKQKVAEDENRNLIDRWMLEKMK DAERLNEANAMYEEMVLKLKSAGVGG IQHNALQEADGIIRRSEAGYMDIMETPIP STCRITIRAHDGGCGSIIFQHNTDKLISG GQDQTVKIWSAHTGALTSTLQGCLGSV NDLAVTNDNKFVIAACSSNKLFVWEVN GGRPRHTLTGHTKNVSSVDASWVKSC VLASSSNDHTIKIWDLQSGFCKSTIMSG SNANSLAFIDGVTLCSGHRDGHLRLWD IRSAKCTSQTFAHLDVSSVSVSRNRNFI LTSGKDNVHNLFDPRTMEVCGKFKAM GNRVVSSWGRPCISPDENSIAAGANDG SVYIWSRLKKDGVPTILQGHSSSVVSSS WCGLGPLATADKHHIYIWT APG9L Os04g0682000 NP_001054293.1 MTSLPDRGVSSSSSDPLCEGNIAPCSSSS 298 [Oryza EQKEDCSLKQSKTSILSCVFNSPFNIFEA sativa HQDSSANKSPKSSSGSYDWSRVLRRIV (japonica CSGSMWRFLGTSKVLTSSDVWFLGKC cultivar- YKLSSEESSSDSDSESGHATFLEDFSSRI group)] WITYRRGFDAISDSKYTSDVNWGCMV RSSQMLVAQALIFHHLGRSWRRPLEKP YNPEYIGILHMFGDSEACAFSIHNLLQA GNSYGLAAGSWVGPYAMCRAWQTLV RTNREQHEVVDGNESFPMALYVVSGD EDGERGGAPVVCIDVAAQLCCDFNKG QSTWSPILLLVPLVLGLDKINPRYIPLLK ETFTFPQSLGILGGKPGTSTYIAGVQDD RALYLDPHEVQMAVDIAADNIEADTSS YHCSTVRDLALDLIDPSLAIGFYCRDKD DFDDFCSRATELVDKANGAPLFTVVQS VQPSKQMYNQDDVLGISGDGNINVEDL DASGETGEEEWQIL APG9L Autophagy- NP_611114.1 MSSPHINYRSLAEEAASPFLEHHPSTGQ 299 specific GPSKTQDAKANAAAAHLDPLGEHGLE gene 9 QPLDEHDTEHEGEDTPRNSGVMIHMVP CG3615-PA ETGRARWNHIEDLDSFFSRMYQYQQK [Drosophila HGFTVIVVDEMLQVLEFGFVVWLLAFV melanogaster] MHCVRFDVLFGDTPPGGLNPNKTTLSD VMYPTGECLANFTWVTYLVVFIAAIYL GIRLLKMVYHITQYADIKRFYNSALHIE DSDLDNFTWHEVQQRIRRVQAEQHMCI DKESLTELDIYHRVLRFKNYLVALMNK QLLPVRFHIPLYGEVVSLSRGMLFNIDFI LFRGPGSPFQNNWQLRDEFAVRSNQTE LAQRLSKLILGVALLNLVLAPVIFVWQL IYFSFSYANILRKEPGALGLRTWSNYGR LYLRHFNELDHELDARLNRAYDYADR YLNSFSSPLAAVIAKNLLFISGGLLLLIL ALGIYEEHVFQVEHLLAILAGLGAIGVV CRTLIPDENLVWCPEQLMTAILAHVHY LPSEWRQQAHTTKVRQEFSNFFQFKAG YLLSEIFSPFVTPFVLIFVFRPKAIELVRF FRTFTVSVRGVGNVCSFAQMDVRKHG NPDWQLTSELEEMTRATAQQPQQEPQQ QSLAGGKTEMSLLRFTLNNPEWQMPK EAKQFLRGVREHAVGELVQAKTSMVQ ENPLTNSLISFGTMGADYCSIANSVLTA QVTPQQLEISQSLRPGLGPVSGGFPVAA SDFRQMLQQNLSASVGPLDSMRRLRLS RAEGRLEGPTDTLLYGLCGVDPRVGST PLNVGVADMCLSALYLHELNQQKRQA RQSRIDEAEDERPGTSHWPPRPPAAPSA DTGFGSRHTVITSKAAESTPLLGSIRS APG9L APG9 NP_850164.1 MMSSGHKGPNVRNFFKWQRGESSSSLT 300 (AUTOPHAGY TGLLHNESHEIELSNYGGIPSPGSESPSG 9) LLNGESLNVQPIADLDLFVERLYSYYRD [Arabidopsis KGLWCIIVKWAVELLSLGFIICFSGFFLL thaliana] YVDWNGLQNAKCGMDAVESGTKPCD LVKEAIHPHPLSPFTLTTAIIVGYLALFS VYWLFCFLRFFAQLKDTLDFRHFYYNN LHVTDNEILTMPWATVLEKVVQLQSSQ CLCVVKDLSAHDMVMRLMRKENYLIG MLNKGLLSFPISHWIPGAGPAVKSAPD GTQYHLVLTKTLEWTLNWCILQSMFDC NFRVRRDFVSNPTTLKKRLFVVGLAML LLSPFLVIFMLVYLFLRHAEQFYNHPST ASSRRWSNLSKWLFREFNEVDHLFKHR INSSVVHASEYLKQFPSPIISIIAKFVSFV SGGFAAVLIIIAFLEESLLEGHIFGRNLF WYAAVFGTITAISRAAISDELLVLDPVG TMSLVVQNTHYMPKRWRGKENKDDV RLELETLFQYTGMMLLEEIASIFITPFLL MFVVPKRVDDILQFIKDFTVDIEGVGH VCSFSAFYFENHGNIKYGSPHNATRRE QRSSQGKMEKSFLSFQSSYPSWESDSLG KQFLSNLRTFRDRKLHEINTRHSSPSRA WRESTNTPALYRDIPRNPLASGNHTDS MWLIDPDQRNHPYLLDWYYTSQAHNR TDHPIERANEILTANQNATDCWPPDLGI RGEDSRDLLNMEASTSGQFFRESILRHD QPEGEDSYGSQHPLDGRNQWWGRGNH SQISTAHPATTNSFIEPPDFINRYTAGNL LDNSWSRRSIEEEDEEEEELDWEENAR RNLSRTTFMDDNDIEAGIDLHFDDVYSS RPQETSTSSTTLR APG9L AuTophaGy NP_872184.1 MAETQNLLQKIDNSSINLIFFQKKTHQM 301 (yeast Atg FNSQSKRAYQQIDDDFDDEVLRNSTCT homolog) SRFMQGWGSSTRSLLFGGASNDEQRNL family IASSSSHHSYHDSPAEEPPETHYEQFTAT member HNHGPPTMASSSQLNSRRWDHVLNLD (atg-9) EFFTHIYEYHQNGGYLCIVLQKVFSLLQ [Caenorhabditis FIFVMSFTTFFTQCVNYQFLFANTNVTS elegans] HGTVNQGKRHFGDAVVDNCPAHISIW MIFAILAAIVYWITRVIKHAQYIMKMSE IQQFYAHELKIADDQLPNLTWHAIVKRI CEAQKKLRLSIHQDNITSIYIYHRILRYK NYMTGMINKRILHPVFDVPFLGPIAYLP NNLKHEIERILFTSSTSAWTNGPNLREE YKHHEQLDMAAKKMKEDVINLFLQILR ISVARPDASTAPIPDYGIVLLTDGAHKK TTRWAWNEKIQYLLRHFNELDHELSAR LNRSHIYAAAYMDQFFSPVLEIAAKNIT FIAAAVFGVLTILSAWDEDVLQVEHVIT VLTICGIVVLVCRGMIPDENLVWQPEIL MTHVTSELHYLPSTWKGKAHTTGVRH EFDQLFQMKWMFFVLELTSPIFTPFVLL FWLRPRCSQLANFFHDYTERVDGLGDV CSFAVMDVGKHGDPKWNHIKELKAIV EDQEDQQQAQSVVTSLNRARDGKTELS ILHFKTTNPEWQPPKASEKFLRKFRNRL GQEASMLAPLTSMHLGQQMDRQQQQ GKIGKK APG9L ADR071Wp NP_984167.1 MEQSEDTIQHERKNTFLSRVFGVHSSEV 302 [Ashbya GDSIETAELSQYPIQIARSGSNAIDESRVI gossypii ESDQASSSEEEDTDGHDLSVAENMTSY ATCC NGAQGSGSEDSDVPFSDQELETIETYTI 10895] AKVGQGSSSEDDRLQADSAEEEDALLF QHRLQDGSKGRNKVSSQPLGLKRILGS KGKSILGKEPASQEDSFIFRKGPTWDEE NQLRPESKRPGLLSGKSNARLSSPSRPS PLSARERALWKWANVENLDGFLQDVY SYYLGNGFYCIMIEKILNLLTLLFIVFIST YMSHCIDYSKLPNGHKFSDVRVDQCYE TQITGTTKLLFWIFGVFVVLKVVQMYF DFRRIHEIHNFYTYLLNISDKELQTIPWQ SVIHQIMRLKDQNAVTANVVEVKAKN HIDAHDVANRIMRKENYLIALYNKDIL HLSLPIPLYRTSTLTKTLEWNIHLCIIGFA FNEAGFLKQSFLNPAQREFLSEELKKRF ILAGFLNIILAPFLVVYFVLLYFFRYFNE YKTSPGSLSTRQYTPIAEWKFREYNELY HLFKKRMGLSYEVANTYINQFPNALGD YFFKFVKFISGSFVAILALMTVLDPENF LNFELTADRTVLFYMTVLGTIWAVCHS AVNDNCSVFDPEDSLKELITYIHYAPKE WDGRYHTDEVKQEFCKLYNLRVILLLR ELASLIMTPFILWFSLPNSAESIVDFFRE VTVYGDGLGYVCKYAMFDENCKKGLR TNKHLQGTQTKYGHSLGDDHDSSDEET DKGMNKMIQSYMYFVDDYQNSVNAV GKYQIPKTQNLSHESKYNMKSHQHYS WKKQFKLGSKPEDFKIGSVTPRALSSSI LANKPKSNLRARLDPEISHSNVQFDDL GESFINSIPVADYDPIERSDAMGGNGVL GLLNQYYRKSDVGR APG9L PREDICTED: XP_001161225.1 MAQFDTEYQRLEASYSDSPPGEEDLLV 303 hypothetical HVAEGSKSPWHHIENLDLFFSRVYNLH protein QKNGFTCMLIGEIFELMQFLFVVAFTTF isoform 3 LVSCVDYDILFANKMVNHSLHPTEPVK [Pan VTLPDAFLPAQVCSARIQENGSLITILVI troglodytes] AGVFWIHRLIKFIYNICCYWEIHSFYLH ALRIPMSALPYCTWQEVQARIVQTQKE HQICIHKRELTELDIYHRILRFQNYMVA LVNKSLLPLRFRLPGLGEAVFFTRGLKY NFELILFWGPGSLFLNEWSLKAEYKRG GQRLELAQRLSNRILWIGIANFLLCPLIL IWQILYAFFSYAEVLKREPGALGARCW SLYGRCYLRHFNELEHELQSRLNRGYK PASKYMNCFLSPLLTLLAKNGAFFAGSI LAVLIALTIYDEDVLAVEHVLTTVTLLG VTVTVCRSFIPDQHMVFCPEQLLRVILA HIHYMPDHWQGNAHRSQTRDEFAQLF QYKAVFILEELLSPIVTPLILIFCLRPRAL EIIDFFRNFTVEVVGVGDTCSFAQMDV RQHGHPQWLSAGQTEASVYQQAEDGK TELSLMHFAITNPGWQPPRESTAFLGFL KEQVQRDGAAASLAQGGLLPENALFTS IQSLQSESEPLSLIANVVAGSSCRGPPLP RDLQGSRHRAEVASALRSFSPLQPGQA PTGRAHSTMTGSGVDARTASSGSSVWE GQLQSLVLSEYASTEMSLHALYMHQLH KQQAQAEPERHVWHRRESDESGESAP DEGGEGARAPQSIPRSASYPCAAPRPGA PETTALHGGFQRRYGGITDPGTVPRALS HFSRLPLGGWAEDGQSASRHPEPVPEE GSEDELPPQVHKV APG9L AGAP001762- XP_321322.4 MTTSRQFDAKTYDTLTNQDTNPFADKR 304 PA SPTIEEEDTPQVIHVVPETSKARWNHIE [Anopheles DLDSFFTRVYIYHQKHGFYVMMLQKLF gambiae str. ELFQFVFVVVLITYMFNCIDYAILFRDKI PEST] IDQESKVSLGDAMIGVSECAANLGAFQ WMALVLAGLFWTFRLFKFFYQFFQFW DIKMFYNTALKIEDADLDNLTWHEVQK CIREVQSEIQMSINKEQLTELDIYHRILR FKNYMVAMMNKSLLPATTKLPLLGNV VLMSQALRYNIGLILFWGPWSPFENSW HLREEYKRPSMRNELAAKLSKQILWVA IANFILSPFIFICQLMYFFFNYADLIKKEP GTLGVRCWSQYGKLYLRHFNELDHEL DARLTRAYRPAVKYMNSFSSPLLTVIA RNIAFDAGGVASLILLLAIYDEDVFQVQ HVLTLFTILGMISVIARSLIPDENMVWC PEQLLRNVLAHVHYLPSVWRGHAHSS VVRDQFELFFQLKIMYILNELFSPLVAP FVLLYDLRPKSQQLVDFFRNFTVDVVG VGDVCSFAQMDVRKHGNPDWQIPVVA DDKDMRPAGAGAGAAAAQYNQGEHG KTELSLVHFTLTNPTWQMPPEAKQFVQ GIKRHALHDLNRQRGMMLGLHNPTAM GQSLLSVESMGAEYSSIIQPILQTHNLSN SQHLGLSMHLGGGGFGSPVPPMTPGYG PAGMMPSTVQQQQQQQPTAQHGGAG VQSSHQYHFGPQSYDFERMLQQNLTD ASTVAPNMPARSTFLADIHENDDESAG APPALMPELEEGSRYAAPYATDGMVYS TRGGMSRREGPAGGSRTGLLSSLYGEL PTNVPAPYEFTTADMCLSTLYLHELHH NHLRRHGGSLRLDMGSPPPPPSSGSSQR PTTTATFSSRFMGPGGIRPSRSMGGSAA AERTPLLGSKKS APG9L unnamed XP_452931.1 MTDSQDKVNGGSKNTFLSRVFGVHSSA 305 protein VENSLDAAEMSHITMPTEQDFSNYAED product EGNVRLIESDQEPSSSNEDSNDEEPLIQQ [Kluyveromyces PQSIRFDTASDGMATIQSESEPDEGGTE lactis] EDEVHLEEEDFSDQDLASSVSKYGQPSS SEDEEPLSNRDSNRGSDETIPFIGRQRLN LGGKNPITGATKSTKNPSESRVFERLLG NSPAKMFRNNGRPNNLEESFLFRKPSV AEQSGPGKSTHFNLKPPPIFNNISTLTST SKNSLSSLSPKERALWKWANIENLDTF LQQVYEYYLGNGFYCIITEKVIHLATILF VVFISTYMGHCIDYSRLSSSHTFEEIHIE QCYKTQISPTAKVFLWIFYAFIGLKVLQ LYFDVKALKDIRNFYNYLLSISDKDLQT IPWQSVIQQLVLLKDQNAITANATEVK AKNRLSAHDVANRIMRKENFVIALYDN NILDLSLPVPLLRTCALTKTLEWNINLCI LGFAFNEKGYLKQAFLRESQREYLGEE LKKRFVLAGFLNIILSPFLVTYFVLLNFF RYFNEYKTSPGSIGSRQYTPIAEWKFRE YNELYHIFQKRMRLSMIIADNYVNQFP NTLLSLTLSFIQFVSGSFVAILGILTIFDP DNFLNFEITPDRTVLFYMTVFGTLWAV CHSSINDEYTVLKPEETLEELVSYTHYA PKEWKGKYHTEDIKNEFCRLYNLRITLL LRELVSIIITPFILWFSLPKNSERIIDFFRE CTVYEEGLGYVCKYAMFEATKIDKGT KAKKQTKRMFSQAEQDDSETESDEGV NKMLQSYMYFVDDYKNAGNAVGKNQ LPASPIEPSYHPYSSTKDYSWKTQFALG KNSNRKRNLNRSRVKRFPDRSSDLELG SLSGSLINKSTLFKDDIADNADELKAGN GVMGLLNQYYKKSDRNR APG9L PREDICTED: XP_536074.2 MAQFDTEYQRLEASYSDSPPGEEDLLV 306 similar HVPEGSKSPWHHIENLDLFFSRVYNLH to QKNGFTCMLIGEVFELMQFLFVVAFTT Autophagy FLVSCVDYDILFANKMVNHSLHPTEPV protein 9- KVTLPDAFLPAQVCSARIQENGSLITILV like 1 IAGVFWIHRLIKFIYNICCYWEIHSFYLH (APG9-like ALRIPMSALPYCTWQEVQARIVQTQKE 1) isoform 2 HQICIHKRELTELDIYHRILRFQNYMVA [Canis LVNKSLLPLRFRLPGLGEAVFFTRGLKY familiaris] NFELILFWGPGSLFLNEWSLKAEYKRG GQRLELAQRLSNRILWIGIANFLLCPLIL IWQILYAFFSYAEVLKREPGALGARCW SLYGRCYLRHFNELEHELQSRLNRGYK PASKYMNCFLSPLLTLLAKNGAFFAGSI LAVLIALTIYDEDVLAVEHVLTTVTLLG VTVTVCRSFIPDQHMVFCPEQLLRVILA HIHYMPDHWQGNAHRSQTRDEFAQLF QYKAVFILEELLSPIVTPLILIFCLRPRAL EIIDFFRNFTVEVVGVGDTCSFAQMDV RQHGHPQWLSGGQTEASVYQQAEDGK TELSLMHFAITNPGWQPPRESTAFLGFL KEQVQRDGAAAGLAQGGLLPENALFTS IQSLQSESEPLSLIANVVAGSSCRGPPLP RDLQGSRHRAEVASALRSFSPLHPGQV PAGRAPSTMTGSGVDARTASSGSSVWE GQLQSLVLSEYASTEMSLHALYMHQLH KQQAQAEPERHVWHRRESDESGESAPE EGGEGSRASQPIPRSASYPCAAPRPGAP ETTALQGGFQRRYGGITDPGTVPRAPS HFSRLPLGGWAEDGQSASRHPEPVPEE GSEDELPPQVHKV APG9L PREDICTED: XP_695180.2 MAHFDTEYQRLEASYSDSPPGEENLLV 307 similar HVPEGSKSPWHHIENLDLFFQRVYNLH to QKNGFTCMLLGEIFELVQLVFVVAFTV autophagy FLANCVDYDILFANKFVNHTDSLKVTL protein 9 PDAFLPVDVCSARIRDSVPVIFILVISGV [Danio FWLHRLVKFIYNICCYWEIRSFYINALKI rerio] SMADLPYFTWQEVQARIVEIQKEHQICI HKKELSELDIYHRILRFKNYMVAMVNK SLLPVRFRLPVLGDTVFYTRGLKYNFEL IFFWGPGSLFENEWSLKSEYKRGGNRL ELADRLSSRILWIGIANLLLCPVILIWQIL YAFFSYTEVIKREPGSLGARCWSLYGRF YLRHFNELDHELMSRLSKGYKASSKY MNCFMSPLLTVVAKNVAFFAGSILAVL IALTIYDEDVLAVEHVLSSITLLGVCITV CRSFIPDKHMVFCPEQLLKVILAHIHYM PDHWQGNAHRYETRDEFAQLFQYKAV FILEELLSPVITPFILIFCLRRKSLEIIDFFR NFTVDVVGVGDTCSFAQMDVRQHGHP AWMSAGKTEASIYQQAEDGKTELSLM HFAITNPHWQPPRESTHFISLLKEKVHR DAAVGQQGIIAENAGFTSTHSLHNDSEP RSLIANLLMGPPSLASLHLGREGSINHV SIGVSEGASALRSLSPVSTSLHLRGSYPS ARLPRSDHPAVVAGRGMAGSGTDARTI SSGSSAWEGQLTSMILSEYASTEMSIHA LYMHEMHKQQSRGELSRHTWHRQESD ESSESVNEDVEAARNFPRSSTFPCTTTS HQEGAAAQQSGSQRRQGGTSDPSSGSF RVQRTPRMAMGGWSEENQTSRHHDPV PEEGSEDELPPHIHKVT BECN1 beclin 1 NP_001006332.1 MEGGRAPACTTQVSFVCQRCSQPLKLD 308 [Gallus TSFKILDRLTIQELTAPPLTAAPARPGDA gallus] QEESALSEEAFTEGRQDGVSRRFIPPAR MMSTESANSFTLIGEASDGGTMENLSR RLKVTGDLFDIMSGQTDVDHPLCEECT DTLLDQLDTQLNITENECQNYKRCLEIL EKMNEDDKEKLQTELKELALEEEQLIQ ELEDVEKNRKIVAEDFERVRAEAERLE QEEAQYQKEYCEFKRQQLELDDELKSV ENQMRYAQMQLDKLKKTNVFNATFHI WHSGQFGTINNFRLGRLPSVPVEWNEI NAAWGQTVLLLHALANKMGLKFQRY RLVPYGNHSYLESLTDKSKELPLYCSG GLRFFWDNKFDHAMVAFLDCVQQFKE EVEKGETRFCLPYRMDVEKGKIEDTGG SGGSYSIKTQFNSEEQWTKALKFMLTN LKWGLAWVSSQFYNK BECN1 beclin 1 NP_001028799.1 MEGSKTSSSTMQVSFVCQRCSQPLKLD 309 [Bos taurus] TSFKILDRVTIQELTAPLLATAQLKPGET QEEEANSGEEPFIETRQDGVSRRFIPPAR MMSTESANSFTLIGEASDGGTMENLSR RLKVTGDLFDIMSGQTDVDHPLCEECT DTLLDQLDTQLNVTENECQNYKRCLEI LEQMNEDDSEQLGLELKELALEEERLIQ ELEDVEKNRKIVAENLEKVQAEAERLD QEEAQYQREYSEFKRQQLELDDELKSV ENQMRYAQMQLDKLKKTNVFNATFHI WHSGQFGTINNFRLGRLPSVPVEWNEI NAAWGQTVLLLHALANKMGLKFQRY RLVPYGNHSYLESLTDKSKELPLYCSG GLRFFWDNKFDHAMVAFLDCVQQFKE EVEKGETRFCLPYRMDVEKGKIEDTGG SGGSYSIKTQFNSEEQWTKALKFMLTN LKWGLAWVSSQFYNK BECN1 beclin 1 NP_001029289.1 MEGSKASSSTMQVSFVCQRCSQPLKLD 310 [Rattus TSFKILDRVTIQELTAPLLTTAQAKPGES norvegicus] QEEEANSGEEPFIETRQDGVSRRFIPPAR MMSTESANSFTLIGEASDGGTMENLSR RLKVTGDLFDIMSGQTDVDHPLCEECT DTLLDQLDTQLNVTENECQNYKRCLE MLEQMNEGDSEQLQRELKELALEEERL IQELEDVEKNRKVVAENLEKVQAEAER LDQEEAQYQREYSEFKRQQLELDDELK SVENQMRYAQMQLDKLKKTNVFNATF HIWHSGQFGTINNFRLGRLPSAPVEWN EINAAWGQTVLLLHALANKMGLKFQR YRLVPYGNHSYLESLTDKSKELPLYCS GGLRFFWDNKFDHAMVAFLDCVQQFK EEVEKGETRFCLPYRMDVEKGKIEDTG GSGGSYSIKTQFNSEEQWTKALKFMLT NLKWGLAWVSSQFYNK BECN1 beclin 1 NP_003757.1 MEGSKTSNNSTMQVSFVCQRCSQPLKL 311 [Homo DTSFKILDRVTIQELTAPLLTTAQAKPG sapiens] ETQEEETNSGEEPFIETPRQDGVSRRFIP PARMMSTESANSFTLIGEASDGGTMEN LSRRLKVTGDLFDIMSGQTDVDHPLCE ECTDTLLDQLDTQLNVTENECQNYKRC LEILEQMNEDDSEQLQMELKELALEEE RLIQELEDVEKNRKIVAENLEKVQAEA ERLDQEEAQYQREYSEFKRQQLELDDE LKSVENQMRYAQTQLDKLKKTNVFNA TFHIWHSGQFGTINNFRLGRLPSVPVEW NEINAAWGQTVLLLHALANKMGLKFQ RYRLVPYGNHSYLESLTDKSKELPLYC SGGLRFFWDNKFDHAMVAFLDCVQQF KEEVEKGETRFCLPYRMDVEKGKIEDT GGSGGSYSIKTQFNSEEQWTKALKFML TNLKWGLAWVSSQFYNK BECN1 beclin 1 NP_062530.2 MEGSKASSSTMQVSFVCQRCSQPLKLD 312 [Mus TSFKILDRVTIQELTAPLLTTAQAKPGET musculus] QEEEANSGEEPFIETRQDGVSRRFIPPAR MMSTESANSFTLIGEASDGGTMENLSR RLKVTGDLFDIMSGQTDVDHPLCEECT DTLLDQLDTQLNVTENECQNYKRCLEI LEQMNEDDSEQLQRELKELALEEERLIQ ELEDVEKNRKVVAENLEKVQAEAERL DQEEAQYQREYSEFKRQQLELDDELKS VENQVRYAQIQLDKLKKTNVFNATFHI WHSGQFGTINNFRLGRLPSVPVEWNEI NAAWGQTVLLLHALANKMGLKFQRY RLVPYGNHSYLESLTDKSKELPLYCSG GLRFFWDNKFDHAMVAFLDCVQQFKE EVEKGETRFCLPYRMDVEKGKIEDTGG SGGSYSIKTQFNSEEQWTKALKFMLTN LKWGLAWVSSQFYNK BECN1 ACR154Wp NP_983556.1 MSTPSFKCQNCQCPIDMDLSLMDLSIA 313 [Ashbya QRDMIVNSGGEPTNPSTFKIPPERLSRL gossypii HQVRRPHELTVAAAPGAAESYVFLQV ATCC NEDGLNRSKHAIEEESGEEEEDDSSKTL 10895] SSNIQVLTNIFNILSSKGNIDYPVCHVCC ELMMQRLKAEYADAIRKRDAYFEFMD RLQKQHEKESAQEPKPASAEADLLAQK DELVTKLVALEHENDKLDKEIESLEQQ LREKEQQETRAVLKQNLKDLEHIAFMK DMQSLKNQYELTLNNLDKLRKTNIFNE TFRISHSGPFGTINDLRLGGFSQVRVPW QEINAAMGQLILLLATIAAKIHYELDGY RLKPLGSYSKVERFDPHTQRWNVYNA YSNDDFKIGKLFHKETSLDKALEAIIAIV DQIAKRISTLSRDHNDGGMELPYSMQK DKINGIPIKLLGSDPTLEWTTSCKFLLTN AKWLLAFSSQVT BECN1 PREDICTED: XP_001160461.1 MEGSKTSNNSTMQVSFVCQRCSQPLKL 314 beclin 1 DTSFKILDRVTIQELTAPLLTTAQAKPG isoform 2 ETQEEETNSGEEPFIETPRQDGVSRRFIP [Pan PARMMSTESANSFTLIGEASDGGTMEN troglodytes] LSRRLKVTGDLFDIMSGQTDVDHPLCE ECTDTLLDQLDTQLNVTENECQNYKRC LEILEQMNEDDSEQLQMELKELALEEE RLIQELEDVEKNRKTVAENLEKVQAEA ERLDQEEAQYQREYSEFKRQQLELDDE LKSVENQMRYAQTQLDKLKKTNVFNA TFHIWHSGQFGTINNFRLGRLPSVPVEW NEINAAWGQTVLLLHALANKMGLKFQ RYRLVPYGNHSYLESLTDKSKELPLYC SGGLRFFWDNKFDHAMVAFLDCVQQF KEEVEKGETRFCLPYRMDVEKGKIEDT GGSGGSYSIKTQFNSEEQWTKALKFML TNLKWGLAWVSSQFYNK autophagy- NP_001002103.1 METKGTDEVETLKSKFMSAWHSVKYS 315 related 4C- WALKSKTAFSRNSPVFLLGKCYHFKVV like [Danio DDENPTESTAEALDDDVVTGNVDEFRK rerio] DFTSRVWLTYREEFPALPGSSFTSDCG WGCTLRAGQMILAQALLLHILGRDWK WSEALSLEPLDTETWTSSAARRLVATL EASIQGERAQASQPLCPVQGEAEEADS YLKETYHRTIVSWFGDGPSAQLGIYKL VELGMTSGKQAGDWYGPAVVAHILRK AVDEAVDAMLKGIRVYVAQDCTVYSA DVIDSHSTRTESHSDPQGLDSGASPDSR AVVILIPVRLGGEKINPEYLNFVKSILSL EYCIGIIGGKPKQAYYFVGFQDDSLIYM DPHYCQSFVDVSTSDFPLQSFHCPSPKK MSFSKMDPSCTIGFYSKSVEHFEKIANE LSKILQPSSKEKYPAFTIMKGHGKDYEL SIAVEKREWPFIRDARKAGTTSGDFVLL microtubule- NP_001004343.1 MPPPQKIPSVRPFKQRKSLAIRQEEVAGI 316 associated RAKFPNKIPVVVERYPRETFLPPLDKTK protein 1 FLVPQELTMTQFLSIIRSRMVLRATEAF light chain 3 YLLVNNKSLVSMSATMAEIYRDYKDE gamma DGFVYMTYASQETFGCLESAAPRDGSS [Homo LEDRPCNPL sapiens] hypothetical NP_001018232.1 MQYLCQRCHSLINFKDVYDDDLLKLK 317 protein NLPKSRFVQASSLTEMNESGESDDQMN SPAC3A12.01c SSSEDYPAQRLQLYKKTISEGDYNFDN [Schizosaccharomyces VPPPELRTPTLDSFVVLPAAKDGYEEEK pombe NSPEEVNDLFSWKIEIYNRIFDLLSSKTK VDHPLCVECAELLTEEMSKTLRALKEE 972h-] KKMYFNYDNFLSSQTVHEENTAALDSE IDELMKQINEKEEKIEEISDETDKLQKLL RELDEEKEKVYAEEQEFYNNLNQFQIK KLSLERQYDCANLEFEHNSRKLEKLQK MNVFSDIFYISHYSEPNGEGSIATINGLR LGRLPSQKVNWAEINAAWGMTVLLLD VLTEKLDFHSSSYQLKPFGSQSFIIRFDR DPNGNQVKPTKLDLFSSGELKIFMNRR FDQGMVAFLDYLHQFGDFCAAKTPSA VLPYAIENDRIGGKCIRLAFNQDENWTR ALKFVLTDIKFLEAYVSSQDKQSNF APG4 NP_001020882.1 MDNTVVMEEIRRLCRASLPCAGAAALS 318 (ATG4) MESERHCNGLPAGAEVTNRPLAWRPL autophagy- VLLIPLRLGLTDINEAYVETLKHCFMMP related QSLGVIGGKPNSAHYFIGYVGEELIYLD homolog B PHTTQPAVELTDSCFIPDESFHCQHPPC [Rattus RMGIGELDPSIAVGFFCKTEEDFNDWC norvegicus] QQVKKLSQLGGALPMFELVEQQPSHLA CQDVLNLSLDSSDVERLERFFDSEDEDF EILSL Transmembrane NP_010132.1 MERDEYQLPNSHGKNTFLSRIFGLQSDE 319 protein VNPSLNSQEMSNFPLPDIERGSSLLHST involved in NDSREDVDENDLRVPESDQGTSTEEED formation of EVDEEQVQAYAPQISDGLDGDHQLNSV Cvt and TSKENVLETEKSNLERLVEGSTDDSVPK autophagic VGQLSSEEEEDNEFINNDGFDDDTPLFQ vesicles; KSKIHEFSSKKSNTIEDGKRPLFFRHILQ cycles NNRPQRDTQKLFTSSNAIHHDKDKSAN between the NGPRNINGNQKHGTKYFGSATQPRFTG pre- SPLNNTNRFTKLFPLRKPNLLSNISVLN autophagosomal NTPEDRINTLSVKERALWKWANVENL structure DIFLQDVYNYYLGNGFYCIILEKILNICT and other LLFVVFVSTYMGHCVDYSKLPTSHRVS cytosolic DIIIDKCYSNSITGFTKFFLWMFYFFVIL punctate KIVQLYFDVQKLSELQNFYKYLLNISDD structures, ELQTLPWQNVIQQLMYLKDQNAMTAN not found in VVEVKAKNRIDAHDVANRIMRRENYLI autophagosomes; ALYNSDILNLSLPIPLFRTNVLTKTLEW Atg9p NINLCVMGFVFNESGFIKQSILKPSQREF [Saccharomyces TREELQKRFMLAGFLNIILAPFLVTYFV cerevisiae] LLYFFRYFNEYKTSPGSIGARQYTPIAE WKFREYNELYHIFKKRISLSTTLANKYV DQFPKEKTNLFLKFVSFICGSFVAILAFL TVFDPENFLNFEITSDRSVIFYITILGAIW SVSRNTITQEYHVFDPEETLKELYEYTH YLPKEWEGRYHKEEIKLEFCKLYNLRIV ILLRELTSLMITPFVLWFSLPSSAGRIVD FFRENSEYVDGLGYVCKYAMFNMKNI DGEDTHSMDEDSLTKKIAVNGSHTLNS KRRSKFTAEDHSDKDLANNKMLQSYV YFMDDYSNSENLTGKYQLPAKKGYPN NEGDSFLNNKYSWRKQFQPGQKPELFR IGKHALGPGHNISPAIYSTRNPGKNWD NNNNGDDIKNGTNNATAKNDDNNGNN DHEYVLTESFLDSGAFPNHDVIDHNKM LNSNYNGNGILNKGGVLGLVKEYYKK SDVGR Autophagy- NP_012041.1 MSSERVLSYAPAFKSFLDTSFFQELSRL 320 related KLDVLKLDSTCQPLTVNLDLHNIPKSA protein and DQVPLFLTNRSFEKHNNKRTNEVPLQG dual SIFNFNVLDEFKNLDKQLFLHQRALEC specificity WEDGIKDINKCVSFVIISFADLKKYRFY member of YWLGVPCFQRPSSTVLHVRPEPSLKGLF the E1 SKCQKWFDVNYSKWVCILDADDEIVN family of YDKCIIRKTKVLAIRDTSTMENVPSALT ubiquitin- KNFLSVLQYDVPDLIDFKLLIIRQNEGSF activating ALNATFASIDPQSSSSNPDMKVSGWER enzymes; NVQGKLAPRVVDLSSLLDPLKIADQSV mediates the DLNLKLMKWRILPDLNLDIIKNTKVLLL conjugation GAGTLGCYVSRALIAWGVRKITFVDNG of Atg12p TVSYSNPVRQALYNFEDCGKPKAELAA with Atg5p ASLKRIFPLMDATGVKLSIPMIGHKLVN and Atg8p EEAQHKDFDRLRALIKEHDIIFLLVDSR with ESRWLPSLLSNIENKTVINAALGFDSYL phosphatidy VMRHGNRDEQSSKQLGCYFCHDVVAP lethanolamine, TDSLTDRTLDQMCTVTRPGVAMMASS required LAVELMTSLLQTKYSGSETTVLGDIPHQ steps in IRGFLHNFSILKLETPAYEHCPACSPKVI autophagosome EAFTDLGWEFVKKALEHPLYLEEISGLS formation; VIKQEVERLGNDVFEWEDDESDEIA Atg7p [Saccharomyces cerevisiae] Subunit of NP_015205.1 MKCQTCHLPLQLDPSLEGLSLTQRNLL 321 phosphatidy LSNNSIITATNENVISNKGIEAADNCGPQ linositol IPKERLRRLGEIQNIKDLNLKDDKLITDS (PtdIns) 3- FVFLNHDDDDNANITSNSREDQRYGNA kinase NGNDNKKANSDTSDGTSTFRDHDEEEQ complexes I EATDEDENQQIQLNSKTLSTQVNAMTN and II; VFNILSSQTNIDFPICQDCCNILINRLKSE Complex I YDDAIKERDTYAQFLSKLESQNKEISES is essential NKEKQYSHNLSEKENLKKEEERLLDQL in LRLEMTDDDLDGELVRLQEKKVQLEN autophagy EKLQKLSDQNLMDLNNIQFNKNLQSLK and LQYELSLNQLDKLRKINIFNATFKISHSG Complex II PFATINGLRLGSIPESVVPWKEINAALG is required QLILLLATINKNLKINLVDYELQPMGSF for vacuolar SKIKKRMVNSVEYNNSTTNAPGDWLIL protein PVYYDENFNLGRIFRKETKFDKSLETTL sorting; EIISEITRQLSTIASSYSSQTLTTSQDESS ortholog of MNNANDVENSTSILELPYIMNKDKING the higher LSVKLHGSSPNLEWTTAMKFLLTNVK eukaryotic WLLAFSSNLLSKSITLSPTVNYNDKTIS gene Beclin GN 1; Vps30p [Saccharomyces cerevisiae] APG4 NP_037457.3 MDAATLTYDTLRFAEFEDFPETSEPVWI 322 autophagy 4 LGRKYSIFTEKDEILSDVASRLWFTYRK homolog B NFPAIGGTGPTSDTGWGCMLRCGQMIF isoform a AQALVCRHLGRDWRWTQRKRQPDSYF [Homo SVLNAFIDRKDSYYSIHQIAQMGVGEG sapiens] KSIGQWYGPNTVAQVLKKLAVFDTWS SLAVHIAMDNTVVMEEIRRLCRTSVPC AGATAFPADSDRHCNGFPAGAEVTNRP SPWRPLVLLIPLRLGLTDINEAYVETLK HCFMMPQSLGVIGGKPNSAHYFIGYVG EELIYLDPHTTQPAVEPTDGCFIPDESFH CQHPPCRMSIAELDPSIAVGFFCKTEDD FNDWCQQVKKLSLLGGALPMFELVEL QPSHLACPDVLNLSLDSSDVERLERFFD SEDEDFEILSL AGP7 [Mus NP_083111.1 MGDPGLAKLQFAPFNSALDVGFWHEL 323 musculus] TQKKLNEYRLDEAPKDIKGYYYNGDSA GLPTRLTLEFSAFDMSASTPAHCCPAM GTLHNTNTLEAFKTADKKLLLEQSANEI WEAIKSGAALENPMLLNKFLLLTFADL KKYHFYYWFCCPALCLPESIPLIRGPVS LDQRLSPKQIQALEHAYDDLCRAEGVT ALPYFLFKYDDDTVLVSLLKHYSDFFQ GQRTKITVGVYDPCNLAQYPGWPLRNF LVLAAHRWSGSFQSVEVLCFRDRTMQ GARDVTHSIIFEVKLPEMAFSPDCPKAV GWEKNQKGGMGPRMVNLSGCMDPKR LAESSVDLNLKLMCWRLVPTLDLDKV VSVKCLLLGAGTLGCNVARTLMGWGV RHVTFVDNAKISYSNPVRQPLYEFEDCL GGGKPKALAAAERLQKIFPGVNARGFN MSIPMPGHPVNFSDVTMEQARRDVEQL EQLIDNHDVIFLLMDTRESRWLPTVIAA SKRKLVINAALGFDTFVVMRHGLKKPK QQGAGDLCPSHLVAPADLGSSLFANIP GYKLGCYFCNDVVAPGDSTRDRTLDQ QCTVSRPGLAVIAGALAVELMVSVLQH PEGGYAIASSSDDRMNEPPTSLGLVPHQ IRGFLSRFDNVLPVSLAFDKCTACSPKV LDQYEREGFTFLAKVFNSSHSFLEDLTG LTLLHQETQAAEIWDMSDEETV APG16 NP_110430.5 MSSGLRAADFPRWKRHISEQLRRRDRL 324 autophagy QRQAFEEIILQYNKLLEKSDLHSVLAQK 16-like LQAEKHDVPNRHEISPGHDGTWNDNQ isoform 1 LQEMAQLRIKHQEELTELHKKRGELAQ [Homo LVIDLNNQMQRKDREMQMNEAKIAEC sapiens] LQTISDLETECLDLRTKLCDLERANQTL KDEYDALQITFTALEGKLRKTTEENQEL VTRWMAEKAQEANRLNAENEKDSRRR QARLQKELAEAAKEPLPVEQDDDIEVIV DETSDHTEETSPVRAISRAATKRLSQPA GGLLDSITNIFGRRSVSSFPVPQDNVDT HPGSGKEVRVPATALCVFDAHDGEVN AVQFSPGSRLLATGGMDRRVKLWEVF GEKCEFKGSLSGSNAGITSIEFDSAGSYL LAASNDFASRIWTVDDYRLRHTLTGHS GKVLSAKFLLDNARIVSGSHDRTLKLW DLRSKVCIKTVFAGSSCNDIVCTEQCV MSGHFDKKIRFWDIRSESIVREMELLGK ITALDLNPERTELLSCSRDDLLKVIDLRT NAIKQTFSAPGFKCGSDWTRVVFSPDG SYVAAGSAEGSLYIWSVLTGKVEKVLS KQHSSSINAVAWSPSGSHVVSVDKGCK AVLWAQY APG10 NP_113670.1 MEEDEFIGEKTFQRYCAEFIKHSQQIGD 325 autophagy SWEWRPSKDCSDGYMCKIHFQIKNGSV 10-like MSHLGASTHGQTCLPMEEAFELPLDDC [Homo EVIETAAASEVIKYEYHVLYSCSYQVPV sapiens] LYFRASFLDGRPLTLKDIWEGVHECYK MRLLQGPWDTITQQEHPILGQPFFVLHP CKTNEFMTPVLKNSQKINKNVNYITSW LSIVGPVVGLNLPLSYAKATSQDERNVP microtubule- NP_115903.1 MPSDRPFKQRRSFADRCKEVQQIRDQH 326 associated PSKIPVIIERYKGEKQLPVLDKTKFLVPD protein 1 HVNMSELVKIIRRRLQLNPTQAFFLLVN light chain 3 QHSMVSVSTPIADIYEQEKDEDGFLYM alpha VYASQETFGF isoform a [Homo sapiens] APG4 NP_116241.2 MEATGTDEVDKLKTKFISAWNNMKYS 327 autophagy 4 WVLKTKTYFSRNSPVLLLGKCYHFKYE homolog C DEDKTLPAESGCTIEDHVIAGNVEEFRK isoform 7 DFISRIWLTYREEFPQIEGSALTTDCGW [Homo GCTLRTGQMLLAQGLILHFLGRAWTW sapiens] PDALNIENSDSESWTSHTVKKFTASFEA SLSGEREFKTPTISLKETIGKYSDDHEM RNEVYHRKIISWFGDSPLALFGLHQLIE YGKKSGKKAGDWYGPAVVAHILRKAV EEARHPDLQGITIYVAQDCTVYNSDVID KQSASMTSDNADDKAVIILVPVRLGGE RTNTDYLEFVKGILSLEYCVGIIGGKPK QSYYFAGFQDDSLIYMDPHYCQSFVDV SIKDFPLETFHCPSPKKMSFRKMDPSCTI GFYCRNVQDFKRASEEITKMLKFSSKE KYPLFTFVNGHSRDYDFTSTTTNEEDLF SEDEKKQLKRFSTEEFVLL APG4 NP_116274.3 MNSVSPAAAQYRSSSPEDARRRPEARR 328 autophagy 4 PRGPRGPDPNGLGPSGASGPALGSPGA homolog D GPSEPDEVDKFKAKFLTAWNNVKYGW [Homo VVKSRTSFSKISSIHLCGRRYRFEGEGDI sapiens] QRFQRDFVSRLWLTYRRDFPPLPGGCL TSDCGWGCMLRSGQMMLAQGLLLHFL PRDWTWAEGMGLGPPELSGSASPSRYH GPARWMPPRWAQGAPELEQERRHRQI VSWFADHPRAPFGLHRLVELGQSSGKK AGDWYGPSLVAHILRKAVESCSDVTRL VVYVSQDCTVYKADVARLVARPDPTA EWKSVVILVPVRLGGETLNPVYVPCVK ELLRCELCLGIMGGKPRHSLYFIGYQDD FLLYLDPHYCQPTVDVSQADFPLESFHC TSPRKMAFAKMDPSCTVGFYAGDRKE FETLCSELTRVLSSSSATERYPMFTLAE GHAQDHSLDDLCSQLAQPTLRLPRTGR LLRAKRPSSEDFVFL autophagy NP_191554.1 MKAICDRFVPSKCSSSSTSEKRDISSPTS 329 4b (APG4b) LVSDSASSDNKSNLTLCSDVVASSSPVS [Arabidopsis QLCREASTSGHNPVCTTHSSWTVILKT thaliana] ASMASGAIRRFQDRVLGPSRTGISSSTS EIWLLGVCYKISEGESSEEADAGRVLAA FRQDFSSLILMTYRRGFEPIGDTTYTSD VNWGCMLRSGQMLFAQALLFQRLGRS WRKKDSEPADEKYLEILELFGDTEASAF SIHNLILAGESYGLAAGSWVGPYAVCR SWESLARKNKEETDDKHKSFSMAVHIV SGSEDGERGGAPILCIEDVTKTCLEFSE GETEWPPILLLVPLVLGLDRVNPRYIPSL IATFTFPQSLGILGGKPGASTYIVGVQED KGFYLDPHDVQQVVTVKKENQDVDTS SYHCNTLRYVPLESLDPSLALGFYCQH KDDFDDFCIRATKLAGDSNGAPLFTVT QSHRRNDCGIAETSSSTETSTEISGEEHE DDWQLL APG5/ATG5 NP_197231.1 MAKEAVKYVWEGAIPLQIHLHKSDVAS 330 (AUTOPHAGY HPAPPPALVLAPRIGYLPLLIPLIKPYFK 5); DSLPPGEDSIWFDYKGFPLKWYIPTGVL transporter FDLLCAEPERPWNLTIHFRGYPCNILIPC [Arabidopsis EGEDSVKWNFVNSLKEAQYIINGNCKN thaliana] VMNMSQSDQEDLWTSVMNGDLDAYT RLSPKLKMGTVEDEFSRKTSLSSPQSQQ VVPETEVAGQVKTARIPVRLYVRSLNK DFENLEDVPEIDTWDDISYLNRPVEFLK EEGKCFTLRDAIKSLLPEFMGDRAQTSG EERSIDDTEEADGSREMGEIKLVRIQGIE MKLEIPFSWVVNNLMNPEFYLHISVLV KAPQR nucleotide NP_199834.2 MVQEEKAMEAINDALRALRKRHLLEE 331 binding GAHAPAISALSKPLISQGSEWKEKTEKL [Arabidopsis ETELQQCYKAQSRLSEQLVIEVAESRTS thaliana] KAILQEKELLINDLQKELTQRREDCTRL QEELEEKTKTVDVLIAENLEIRSQLEEM TSRVQKAETENKMLIDRWMLQKMQDA ERLNEANDLYEEMLAKLKANGLETLA RQQVDGIVRRNEDGTDHFVESTIPSTCA NRIHAHEGGCGSIVFEYNSGTLFTGGQD RAVKMWDTNSGTLIKSLYGSLGNILDM AVTHDNKSVIAATSSNNLFVWDVSSGR VRHTLTGHTDKVCAVDVSKFSSRHVVS AAYDRTIKLWDLHKGYCTNTVLFTSNC NAICLSIDGLTVFSGHMDGNLRLWDIQT GKLLSEVAGHSSAVTSVSLSRNGNRILT SGRDNVHNVFDTRTLEICGTLRASGNR LASNWSRSCISPDDDYVAAGSADGSVH VWSLSKGNIVSILKEQTSPILCCSWSGIG KPLASADKNGYVCTWT autophagy- NP_443168.2 MESVLSKYEDQITIFTDYLEEYPDTDEL 332 related VWILGKQHLLKTEKSKLLSDISARLWFT cysteine YRRKFSPIGGTGPSSDAGWGCMLRCGQ endopeptidase MMLAQALICRHLGRDWSWEKQKEQPK 2 isoform EYQRILQCFLDRKDCCYSIHQMAQMGV a [Homo GEGKSIGEWFGPNTVAQVLKKLALFDE sapiens] WNSLAVYVSMDNTVVIEDIKKMCRVL PLSADTAGDRPPDSLTASNQSKGTSAY CSAWKPLLLIVPLRLGINQINPVYVDAF KECFKMPQSLGALGGKPNNAYYFIGFL GDELIFLDPHTTQTFVDTEENGTVNDQT FHCLQSPQRMNILNLDPSVALGFFCKEE KDFDNWCSLVQKEILKENLRMFELVQK HPSHWPPFVPPAKPEVTTTGAEFIDSTE QLEEFDLEEDFEILSV AuTophaGy NP_490885.2 MDYEVCRKVWESHVPCQFTLQSSGGT 333 (yeast Atg HGEPLPFYTMLPRFSYLALAIQKVLSSF homolog) NRRDDGEKVHSDKMWLEHNGIPLKMY family IPIGVIYDQANLSENDSILEIIVRTSQPPP member QFQMVDRDMMEAMFMQNIKEADYLK (atg-5) TKAEITKNMMKDESAQLWRSVCNNNF [Caenorhabditis DEFWTIVQKLMETSEGNEFAHIPLRVY elegans] VKNQAFKQALITAKHPDGSLRTIGEAVS DVLSSSSSSSTDSQSEHPPRLISHGIDIPH HTPLIFAAKNLSYPDNFIHVVLLLVVP AuTophaGy NP_500024.1 MQNLVNNLKSAALQIGETFTPVLRESK 334 (yeast Atg FRETGVLTPEEYVAAGDHLVHHCPTW homolog) KWAGASDPSKIRTFLPIDKQFLITRNVP family CHKRCKQMEYDEKLEKIINEEDGEYQT member SDETGWVDTHHYEKEHEKNEEKEQST (atg-3) APPPAAPEDSDDDDEEPLDLDELGLDD [Caenorhabditis DEEDPNRFVVEKKPLAAGNDNSGEVEK elegans] VRTYDLHICYDKYYQVPRLFLMGYDE NRRPLTVEQTYEDFSADHSNKTITVEAH PSVDLTMPTVHPCKHAEMMKRLINQY AESGKVLGVHEYLFLFLKFVQAVIPTIE YDYTRAIKL BEClin NP_500844.1 MTTQRSHICLNCQHPLRLDFTQRRPDS 335 (human ADSEKKSETVITEALTGHSRNLMKLISD autophagy) AQFPSDAPVCNDCSDALRNEMDAQVA homolog TLDDEIKTYQTYINYLKENHPTTSIPDLK family AKLQNVSDEEKELEQQLKKLLAEEEQL member DLDLQTKRRTAEAASEKSGELWKKYR (bec-1) DNLRQVFEDQDELHSLEAERQYAEVQH [Caenorhabditis RKLTDTNVLDLCFHIWVDGIVGEINGFR elegans] LGYLKDAPVEFTEINAALGQIVLLLEILL ERIGVQHHELMPVAMGSHSYIKLRRNG IDMETYALYGQGTPLSGSSGIDPGIRRF LQLLEFLLKELKDRNKNFKPPYQIHADS LVDNGVKYNAVMTLNTDVRWTRAMA LMLTDLKAACAQCDALRSPI LC3, NP_502035.1 MSGNRGGSYISGIVPSFKERRPFHERQK 336 GABARAP DVEEIRSQQPNKVPVIIERFDGERSLPLM and GATE- DRCKFLVPEHITVAELMSIVRRRLQLHP 16 family QQAFFLLVNERSMVSNSMSMSNLYSQE member RDPDGFVYMVYTSQPAFG (lgg-2) [Caenorhabditis elegans] AuTophaGy NP_502208.1 MNNIPDDFKKIASSSRLPRKYCSSESSLS 337 (yeast Atg DDDGHEIEHVLKHGAPEEALTPDTERM homolog) VVLGQDVVQSAPASLVPGGNLSWMSK family IKSAGASMMGSIRPSSSSQDVHSTGEIE member KHSKKKWKARLWSTWNNIKYSSTWM (atg-4.2) SDRSDEYGGENDVVFLGRRYSTSVDES [Caenorhabditis GLRSGFENFCSDYYSRLWITYRTDFPAL elegans] LDTDTTTDCGWGCMIRTTQMMVAQAI MVNRFGRDWRFTRRKRSHVAAHGDED DFDREKIQEWMILKLFEDKPTAPLGIHK MVGIAAMGKGKKAVGSWYSPSEAVFI MKKALTESSSPLTGNTAMLLSIDGRVHI RDIEVETKNWMKKLILVIVVRLGAAEL NPIYVPHLMRLFAMESCLGITGGRPDHS SWFVGYYGDQIIYLDPHVAHEYIPIDINP NTNVVDSDSKKAKKCPEKSYHCRLLSK MHFFDMDPSCALCFQFESREQFDNDMR QLNLSQFIDIDQGEEHGMKRVRDPMFS VVYGERRQPPSYEREVSETEQAQADKH GFEML AuTophaGy NP_508768.1 MQTRSIDNVVNWSRCVHPSCVAWVIFI 338 (yeast Atg HFCFAKNCSILYFVLFQFTFFAELMADS homolog) YRKLIIERLEDVKQRNKQTATLYNNYS family KLAEQLEKKHKYGTSSSNSSQLETGEL member ARVKEEMAELYRSKCQNDQRLIDANH (atg-16.1) RIADFEKKSSAIIAEKIALEATAKSICAK [Caenorhabditis YAKTEVELQRLKVDNDQLNDERIASNT elegans] TVTMLTKQIQDIENDRIHFLNKIRELNE QRVDFLNAEVALEEKRRNSRIQDMITS AVQDITDKDTKLEEMLRAMPDTNSNG DLLLGDSVPSRAEFVLECEEGEVNDVH WLDGETFATGGSDRNIKIWKVDGHGG YTRIGTLAGSNAAFTRIDYERDRKHFIA SSNDKNVRIWNLDNSRLLSTLSGHSDQ VTCVKFYQSHSAVSGSADRVIKIWDIQ NQRCSRSLFPASKVLDVATNMGASPSL FASGHFDKKLRFYDGRSTDPVRTVDM GGRITSLDVTMSGCELLVSTRDDTISLID LRTFQTVHCYSAENYRTSSDLSRVVLSS GNEYVAAGSSNGSIFVWNRNSTKLEKQ LCSNSENAIFSLSWNPTGYGLLSSSKQK FVTLWK autophagy NP_567116.1 MRKEEIPDKSRTIPIDPNLPKWVCQNCH 339 protein HSLTIVGVDSYAGKFFNDPPPSATQGSS Apg6 IHGANSVLGSTRMDNSFVVLPRHKPPQ family SQGIPPRPRGASSPQPDATQSGKAMEES [Arabidopsis FVVVYKSEPVSDSGGSHNLSLEVGQNG thaliana] PLHSNTSGFNATINVLTRAFDIARTQTQ VEQPLCLECMRVLSDKLEKEVEDVTRD VEAYEACVQRLEGETQDVLSEADFLKE KKKIEEEERKLVAAIEETEKQNAEVNH QLKELEFKGNRFNELEDRYWQEFNNFQ FQLIAHQEERDAILAKIEVSQAHLELLN KTNVLIDAFPIRNDGEFGTINNFRLGRLP AIKVEWDEINAAWGQACLLLHTMCNY FRPKFQCQVKIQPMGSYPRIVDSNNETY ELFGPVNLFWSTRYDKAMTLYLMCLK DFADFANSKDQENNIPPDNCLNLPYKIE KDKVLGYSITQSFNKQESWTKALKYTL CNLKWALYWFVGNTNFQPLSATVSLPS NISAAGSLYAKRGPDSSKPSCKKT APG7 NP_568652.1 MAEKETPAIILQFAPLNSSVDEGFWHSF 340 (AUTOPHAGY SSLKLDKLGIDDSPISITGFYGPCGHPQV 7) SNHLTLLSESLPLDEQSLIASTSHGNRN [Arabidopsis KCPVPGILYNTNTVESFNKLDKQSLLK thaliana] AEANKIWEDIQSGKALEDPSVLPRFLVI SFADLKKWSFRYWFAFPAFVLDPPVSLI ELKPASEYFSSEEAESVSAACNDWRDS DLTTDVPFFLVSVSSDSKASIRHLKDLE ACQGDHQKLLFGFYDPCHLPSNPGWPL RNYLALIRSRWNLETVWFFCYRESRGF ADLNLSLVGQASITLSSGESAETVPNSV GWELNKGKRVPRSISLANSMDPTRLAV SAVDLNLKLMRWRALPSLNLNVLSSV KCLLLGAGTLGCQVARTLMGWGIRNIT FVDYGKVAMSNPVRQSLYNFEDCLGR GEFKAVAAVKSLKQIFPAMETSGVVM AIPMPGHPISSQEEDSVLGDCKRLSELIE SHDAVFLLTDTRESRWLPSLLCANANK IAINAALGFDSYMVMRHGAGPTSLSDD MQNLDINKTNTQRLGCYFCNDVVAPQ DSMTDRTLDQQCTVTRPGLAPIAGALA VELLVGVLQHPLGINAKGDNSSLSNTG NNDDSPLGILPHQIRGSVSQFSQITLLGQ ASNSCTACSETVISEYRERGNSFILEAIN HPTYLEDLTGLTELKKAANSFNLDWED DDTDDDDVAVDL autophagy 3 NP_568934.1 MVLSQKLHEAFKGTVERITGPRTISAFK 341 (APG3) EKGVLSVSEFVLAGDNLVSKCPTWSWE [Arabidopsis SGDASKRKPYLPSDKQFLITRNVPCLRR thaliana] AASVAEDYEAAGGEVLVDDEDNDGWL ATHGKPKDKGKEEDNLPSMDALDINEK NTIQSIPTYFGGEEDDDIPDMEEFDEAD NVVENDPATLQSTYLVAHEPDDDNILR TRTYDLSITYDKYYQTPRVWLTGYDES RMLLQPELVMEDVSQDHARKTVTIEDH PHLPGKHASVHPCRHGAVMKKIIDVLM SRGVEPEVDKYLFLFLKFMASVIPTIEY DYTMDFDLGSSST Autophagy- NP_572390.1 MAHDREVLRMIWEGQIGICFQADRDEI 342 specific VGIKPEPFYLMISRLSYLPLVTDKVRKY gene 5 FSRYISAEHQDGAVWFDFNGTPLRLHY CG1643-PA PIGVLYDLLHPEEDSTPWCLTIHFSKFPE [Drosophila DMLVKLNSKELLESHYMSCLKEADVL melanogaster] KHRGLVISAMQKKDHNQLWLGLVNEK FDQFWAVNRRLMEPYGDLESFKNIPLRI YTDDDFTYTQKLISPISVGGQKKSLADL MAELSTPVRRAVGCRTHGIDLHEETQL QWMSEHLSYPDNFLHLSVDYKDV ubiquitin- NP_596084.1 MFVGKALQFQSFHSSIDATFWHQLSNY 343 like KVEKQKLDASPLTIHGKFNTYSRGNISI conjugating VFGEAPSNSNIKDCLAEGTLLNANTPQE enzyme FTNADVKKIREEIGEVLLNSIKNGVVSE [Schizosaccharomyces RPNELLRFLIFSYADIKAYKYHYWCLFP pombe SFKETPHWIVKDLSPAESLIPSGPILSQIR 972h-] EFLSTADYYQRPFFLLIKSTLDEWTIAPL KELSHCVDKSLQFYLVAEDSVQLAEYP SWPVRNILAFAFIKFKLKVINLFLYRDGI NSDTLSKSILIKVEADKDMILEAPLSIVG WERNGKGVLGPRVVNLSTVLDPFVLSE SASTLNLSLMRWRLVPQLDLDRIQNSK CLLLGAGTLGCGVARNLLSWGVRHVT FVDYSTVSYSNPVRQSLFTFEDCKRKLP KAECAAQRLKEIYPNMFSTGYNISIPML GHPIYEAGIEKTMHDYETLENLISTHDA IFLLTDTRESRWLPTVISTAMDKLLINSA LGFDSWLVMRHGSVLQKENRLGCYFC NDIFAPSNSLVDRTLDQTCTVTRSGCAN IATAIAVELFVSLLQHPNGHAAPVLNED QTVLGELPHQIRGFLHNFSLMKISGMA YPQCSACSECIINEWNREKWMFVLRAI NEPDYVEELCGLREVQALGEIAGTMEE WISDKESVIL autophagy NP_596247.1 MFYQPAQNKKQYDDLADIEAQNNVPN 344 associated TQEVLEAWQESLDSDEDESSPLEESNGF protein TISEHDDFVKSVPRKNNPTDLLYSGKLL Atg9 DSDEPPSVHGNSSKVPSKHPSPSFPETTS (predicted) LRNLQNGSKQKPALPNFNDPHFYNEDV [Schizosaccharomyces TRSGHPNRSIYTQLPRNEFSNARVLWN pombe] RLSARDRVLWRWANVENLDSFLQQVY TYYTGKGLSCIIVHRLFQILTVSFVIGFT TFITSCIDWPAVTPHGSLAGVTKSQCIA QMSPITYLVLWLFLSFLLALWIYYLTDI PRLWQMREFYIHALKIATADMPTVSWQ RVLYRLLKLKNVNALTAEDGRVVSLH NMKRLDAYAIANRIMRKDNYFIALINN GIINIELPLLHRRILTHTTEWNINWCIFNF VFDEQGQLRSAFRNPNSRKRLSEELRR RFIVAGFLNCLFAPIVAIYLVIHNFFRYF NEYHKNPGALSTRRYTPLALWTFREYN ELQHFFDERINDSYAAASHYVSQFPDFN MIRLFKYISFILGSFTAILVIITVFDPELM VTFEITKDRSVLFYLGLFGSLIAVSRSIIP DETLVFAPEKALRRVITFTHYMPGWWS DNMHSKAVQQEFCSLYSYRIVNLLWEI LGILLTPVLLFFTFPSCSQDIVDFFREHTI NVEGVGYVCSYAVFQDNPPYESVASLV QSRKISPLIQNKPELSRISFYEQFNTEAP RRDLR Autophagy- NP_608563.1 MLVGLSDQLARIMESVFEAYLGPDSVL 345 specific ASAVGQAVGSGEPEDIPRRNTDVWVLG gene 4 KKYNAIQELELIRRDIQSRLWCTYRHGF CG4428-PA SPLGEVQLTTDKGWGCMLRCGQMVLA [Drosophila QALIDLHLGRDWFWTPDCRDATYLKIV melanogaster] NRFEDVRNSFYSIHQIAQMGESQNKAV GEWLGPNTVAQILKKLVRFDDWSSLAI HVAMDSTVVLDDVYASCREGGSWKPL LLIIPLRLGITDINPLYVPALKRCLELDSS CGMIGGRPNQALYFLGYVDDEVLYLDP HTTQRTGAVAQKTAAAEQDYDETYHQ KHAARLNFSAMDPSLAVCFLCKTSDSF ESLLTKLKEEVLSLCSPALFEISQTRAVD WDTTEDIDWPTMPDIDWPAGTSDSDSF AIVEESGRDSDAGCSGAIGSGKKPSERA VI Autophagy- NP_611350.1 MSTEKEIILQFAPWESFVSPTFWHKLAE 346 specific LKLDHDRLSDSKRSITGHYTNRNASGC gene 7 LLEVDYTAYNRMAKPPKFSHSAIGTIY CG5489- NKNTIEEFKALDKLQLLADEGKELLAD PA, isoform A MCSGGALRDPSLLTRFFVLSFADLKCH [Drosophila SYYYWFAFPCPLTPTLKLQGAVQKLRD melanogaster] LPNSSSYIMALKALPTESQNFFILYANV EKNIFEARSLSSLDDKNVEFCYFGFADP SEYEHPAWIMRNYAAFLLQQCPSFVGK PLKFLGLRHNQQMNIDDSLVWKVIQTE ACDLSQSENIKFVGWELNKNGKMGPR MVCMRDSMDPAKLAENSVNLNLKLM KWRLVPDLNLEIISQTKCLLFGAGTLGC AVARNLLSWGFKHITLLDSGKVGFSNP VRQNLYTHADAVAGNRMKATTAAQR LKEINPSAETAGYVLEIPMPGHTIGESLL AQTKEHLKVIEKLVQDHDVIFLLTDSRE SRWLPTLLGAAKEKIVINAALGFDSYLV MRHGTTRKEAGDDGQEIEGLKCINGDQ LGCYFCNDVTAPGNSLKDRTLDQQCTV TRPGVSNIAASYAVELLVALLQHPRKEL APAYYAQSGRGRSEETEEKVPEGLLGIL PHSIRGMLCNYENILPATQKFAQCIACS AAVLNEYKKEGHAFLFKTFETAKFLED LTGISEFKRLNSEIIDFDDEEFDMSDSDED Autophagy- NP_651209.1 MSEAEKQAVSFACQRCLQPIVLDEQLE 347 specific KISVHAMAELSLPIYGDNGNTLDPQDA gene 6 SSFDHFVPPYRLTDSINGTGFMLVSDGR CG5429-PA DNKKMSAAFKLKAELFDCLSSNSEIDH [Drosophila PLCEECADSMLEIMDRELRIAEDEWDV melanogaster] YKAYLDELEQQRVAPNVEALDKELDEL KRSEQQLLSELKELKKEEQSLNDAIAEE EQEREELHEQEESYWREYTKHRRELML TEDDKRSLECQIAYSKQQLDKLRDTNIF NITFHIWHAGHFGTINNFRLGRLPSVSV DWSEINAAWGQTVLLLSALARKIGLTF ERYRVVPFGNHSYVEVLGENRELPLYG SGGFKFFWDTKFDAAMVAFLDCLTQF QKEVEKRDTEFLLPYKMEKGKIIDPSTG NSYSIKIQFNSEEQWTKALKFMLTNLK WGLAWVSSQFVSP CG31033 NP_733313.2 MSTEEHVWRAHVVRRLRERNRKECDN 348 CG31033- FKEIIEQNNRLIDHVAQLKADNLKISVE PC, isoform C NEQLRNAVSTGGTGSNVAIATLEKKLL [Drosophila SQQEELTELHKRKGENSQMIVDLNQKV melanogaster] EQQRIIISEKEHSLVEQQTNNNRLRAEV QLLHSSLEELKKLNNTMLDEHTALQLA FSSLEEKLRGVQDENRRLLERLMQYKS KDADKLNEENESIIRKRSAKLKRDLEDA VREPSSSSNAASSPGAASLQRNSSPAQF VGGLIGDEDFDEAAINGAMEAIGLDDN EYISARFTAGEIAENSRASIDTLKATGYL GQANPTKILMKFEAHENESHAVRWSPV ERMVATGGADRKVKLWDIGKNSTEPR AVLSGSSAGINSVDFDSTGAYILGTSND YGARVWTVMDNRLRHTLTGHSGKVM AAKYVQEPIKVVTGSHDRTLKIWDLRSI ACIETKFAGSSCNDLVTTDSLGSTIISGH YDKKIRFWDIRTEKQADDVLMPAKITS LDLSKDCNYLICSVRDDTIKLLDLRKNQ VISTFTNEHFKISCDFARASFNSSGLKIA CGSADGAIYIWNVNGFLEATLKGHSTA VNAVSWSPNNNMLASVGKNKRCTIYS ES autophagy NP_850412.1 MKALCDRFVPQQCSSSSKSDTHDKSPL 349 4a (APG4a) VSDSGPSDNKSKFTLWSNVFTSSSSVSQ [Arabidopsis PYRESSTSGHKQVCTTRNGWTAFVKRV thaliana] SMASGAIRRFQERVLGPNRTGLPSTTSD VWLLGVCYKISADENSGETDTGTVLAA LQLDFSSKILMTYRKGFEPFRDTTYTSD VNWGCMIRSSQMLFAQALLFHRLGRA WTKKSELPEQEYLETLEPFGDSEPSAFSI HNLIIAGASYGLAAGSWVGPYAICRAW ESLACKKRKQTDSKNQTLPMAVHIVSG SEDGERGGAPILCIEDATKSCLEFSKGQ SEWTPIILLVPLVLGLDSVNPRYIPSLVA TFTFPQSVGILGGKPGASTYIVGVQEDK GFYLDPHEVQQVVTVNKETPDVDTSSY HCNVLRYVPLESLDPSLALGFYCRDKD DFDDFCLRALKLAEESNGAPLFTVTQT HTAINQSNYGFADDDSEDEREDDWQML ATG10 NP_850533.1 MDSAREVSDGRLTVEGFSVASRAFADK 350 (AUTOPHAGY WKIHNQSFPPWSWVPLINRTLLVSKKQ 10); EEGYLSLEKIIILSSLEEEIPEDESLNVAT transporter DCLEKEETVDHTILVPTMENEAHYYDF [Arabidopsis HIVYSASYKVPVLYFRGYCSGGEPLAL thaliana] DVIKKDVPSCSVSLLLESKWTFITQEEH PYLNRPWFKLHPCGTEDWIKLLSQSSSS SGCQMPIVLYLVSWFSVVGQVVGLRIP LEMLN microtubule- NP_956592.1 MPPFEKTPHPKPFKQRKSLATRKQEVA 351 associated GIRTKFPTKIPVIIERYQREKFLPPLDKT protein 1- KFLVPQELTMTQFVTIIRNRMTLMPNQ light chain AFYLLINNSGIASMSMTMAQLYKDHKD 3C [Danio EDGFLYMTYASQEMFGHR rerio] AER298Cp NP_985155.1 MSQSLKFAPPFQSFVDASFFQVFSRLKL 352 [Ashbya DVLRLDSHELPLHAKVDLAGLARGSSIS gossypii HVFLDSQSFDEATASLPGISLRGSFFNFN ATCC TLEEFKRLDKGRFLSEQAQLLWEAGVN 10895] GYLDEAAGFFVICFADLKKYRFYYWFA TPCFQPETLELKVVKREALTEIDKFSNFI EQNKILCGVLNEETGEVIRASRHELERY STLVVRDTSNIEHCPTSLVKNFVAVWR HHNPNRSECRVLLLRETCSFSLELSVTG DAMSTSQLKASGWERNVRGLLTPKISE LGAIIDPTKLAEQSIDLNLKLMKWRLVP DINLDIVKNCKVLLLGAGTLGCYVARS LLAWGVRKITFVDNGSVSYSNPVRQPL FNFTDCGQPKATSAAAAMKAIFPLVDA TGFQLEVPMIGHPLTDEARQKKDYEEL RQLIRDHDIVFLLMDSRETRWLPTILGN LESKLVINAALGFDSYLVMRHGNYEQP ESSRLGCYFCHDVVAPSDSLTDRTLDE MCTVTRPGVALIAAAYATELAVSVLQH PQGNNAPETSESVLGSVPHQLRGFLPQL STVKLRTPAYKHCSACSSVIVDAVREN GWEFLREALVDHRIVERLSGLAQVQQE TETFLATMEISDDDCFDEIS PREDICTED: XP_001126088.2 MDAATLTYDTLRFAEFEDFPETSEPVWI 353 similar LGRKYSIFTEKDEILSDVASRLWFTYRK to APG4 NFPAIGGTGPTSDTGWGCMLRCGQMIF autophagy 4 AQALVCRHLGRDWRWTQRKRQPDSYF homolog B SVLNAFIDRKDSYYSIHQIAQMGVGEG [Homo KSIGQWYGPNTVAQVLKKLAVFDTWS sapiens] SLAVHIAMDNTVVMEEIRRLCRTSVPC AGATAFPADSDRHCNGFPAGAEVTNRP SPWRPLVLLIPLRLGLTDINEAYVETLK HCFMMPQSLGVIGGKPNSAHYFIGYVG EELIYLDPHTTQPAVEPTDGCFIPDESFH CQHPPCRMSIAELDPSIAVGFFCKTEDD FNDWCQQVKKLSLLGGALPMFELVEL QPSHLACPDVLNLSLGESCQVQVGSLG DSSDVERLERFFDSEDEDFEILSL PREDICTED: XP_001153028.1 MEIFIVKRVWEQRVEDVRLIREQHPTKI 354 similar PVIIERYKGEKQLPVLDKTKFLVPDHVN to MSELIKIIRRRLQLNANQAFFLLVNGHS microtubule- MVSVSTPISEVYESEKDEDGFLYMVYA associated SQETFGMKLSV proteins 1A/1B light chain 3 [Pan troglodytes] PREDICTED: XP_001333093.2 MNSVSPSAVQYIVGGGAHEDKASASSK 355 similar RHLGHGAVPDGIREGSGEPDEVDRLKA to APG4-D KFMSAWNNVKYGWTVKSKTSFNKSSP protein LILLGQSFLFNNEGEVERFRQTFVSCVW [Danio LTYRREFPQLDGSSLTTDCGWGCMLRS rerio] GQMMLAQGLLLHLMPTDWRWSDCHA LTDVDFEVLKPRSPSRPAGMSMPSFSSS WSSSIPQINPSPGITEAHRRAPARCPSAS PDPQVDALHRKVVSCFGDHPSAPFGVH QLVELGKESGKRAGDWYGPSVVAHML RKAVARAAEFEDLAVYVAQDCTVYKE DVMSLCESSGVGWKSVVILVPVRLGGE SLNPSYIECVKNILKLKCCIGIIGGKPKH SLFFVGFQDEQLLYLDPHYCQPVVDVT QANFSLESFHCNSPRKMNFSRMDPSCTI GLYARSKTDFESLCTAVSEALSSSKEKY PIFTFVEGRGQIYGMEGPSGGSVDAPAH IFTCSRLSRNNKRGSTDEFVLL PREDICTED: XP_001345056.1 MAHFDTEYQRLEASYSDSPPGEENLLV 356 similar HVPEGSKSPWHHIENLDLFFQRISFNGF to TCMLLGEIFELVQLVFVVAFTVFLANC autophagy VDYDILFANKFVNHTDSLKVTLPDAFL protein 9 PVDVCSARIRDSVPVIFILVISGVFWLHR [Danio LVKFIYNICCYWEIRSFYINALKISMADL rerio] PYFTWQEVQARIVEIQKEHQICIHKKEL SELDIYHRILRFKNYMVAMVNKSLLPV RFRLPVLGDTVFYTRGLKYNFELIFFWG PGSLFENEWSLKSEYKRGGNRLELADR LSSRILWIGIANLLLCPVILIWQILYAFFS YTEVIKREPGSLGARCWSLYGRFYLRH FNELDHELMSRLSKGYKASSKYMNCF MSPLLTVVAKNVAFFAGSILAVLIALTI YDEDVLAVEHVLSSITLLGVCITVCRSFI PDKHMVFCPEQLLKVILAHIHYMPDHW QGNAHRYETRDEFAQLFQYKAVSHGV FILEELLSPVITPFILIFCLRRKSLEIIDFFR NFTVDVVGVGDTCSFAQMDVRQHGHP AWMSAGKTEASIYQQAEDGKTELSLM HFAITNPHWQPPRESTHFISLLKEKVHR DAAVGQQGIIAENAGFTSTHSLHNDSEP RSLIANLLMGPPSLASLHLGREGSINHV SIGVSEGASALRSLSPVSTSLHLRGSYPS ARLPRSDHPAVVAGRGMAGSG AGAP007296- XP_308525.2 MAEEAEATGIDNNSEKDLATNVENLSL 357 PA TNQKVEKQESKKIDIVLHATGSAPILKQ [Anopheles KKWAVDQEKPISAIVKFIHKYLKLDAE gambiae str. ERLFLYINQTFAPSPDQIIKNLYECYGTN PEST] GKLILHYAKTQAWG AGAP010939- XP_309756.4 MANDREILREIWEGKIPVHFKLSADETD 358 PA VEPEEYFLLIPRLSYFPLVTDKVRKHFL [Anopheles RFVSNELQDGEMWMDSNGTPLKWHFP gambiae str. IGVLYDLLVGTDGTLPWHVTVHFSKFP PEST] DDILIRCPNKEIVEAHFMSSLKEADVLK HRGQVVSAMQKKDHNQLWLGLVNDK FDQFWAVNRRLMEPIPDQDGFKHIPVR CYAEDGTYQQKLVAPSTASGQKRLLQ DLLDDFSTPVRKAVEARTHGVTVPEST PLQWLSEHLSYPDNFLHLCLSYA AGAP003858- XP_310418.5 MNDAKVSVSFSCQRCMQPIHVDDTFAS 359 PA LGEHTLAELALPINSHLEVDLESQSVSF [Anopheles DHFVPPFRVTDSTNDTNGFMLLSDGQN gambiae str. KESLGHSLRVKAELFDALSNNSEIDHPL PEST] CDECTDTLLELMDKQLKIAEDEWNDY NNYLKKLEMTDDVPNIDELEQELAGLK EDETRLLEELSSLSREEQSIRQAVEEQEK EKQRLEREENKYWREYTKHRRDVITTE DEFRSLECQMAYAQSQLEKLKKTNVFN ATFHIWHSGHFGTINNFRLGRLPSAPVD WSEINAAWGQTCLLLSALARKMNFSFK QYRLVPYGNHSYIEVLGEGKELPLYGN GGFRFLWDSKYDAAMVAFLDCLQQFK EEIVRRDPDFCLPYLMEKGKIEDASTGS SFSIKIQFNSEEQWTKALKYLLTNLKWV LTWVSSQFTEDKQR AGAP002319- XP_312653.3 KLLLICRLFSSFLPQHTLTGHSGKVLAA 360 PA KFLGSAFLVTGSHDRTLKIWDLKNRSC [Anopheles TETKFAGSSCNDLVTTDSFSFISGHVDK gambiae str. KIRFWDVRTADCTANDIPLQGKITSLDL PEST] SKDGKFLLSCVRDDTINLLDLRQNRIVR TFRNDNFKVGCDWSRVAFSPSSSRIAA GSADGSVYIWNINGPLETVLKDPNGSG AAVTAVSWHPFSSTLASVDRAKKCTIW SNA AGAP008497- XP_316946.4 GKMLDAYVGYDLSIATEPDDIPKTNDT 361 PA VWILGKQYNASDDLEAIRQDVQSRLW [Anopheles CTYRRGFVPIGNTQLTTDKGWGCMLR gambiae str. CGQMVLAQALLQLHLGRDWVWEAET PEST] RDDIYLNIVNRFEDSKQAPFSLHQIALM GDSSEEKRIGEWFGPNTVAQVLKKLVK FDDWCRLVIHVALDNTVATDEIVELCV DKKEPEAWKPLLLIIPLRLGLSEVNPIYI EGLKKCFQLPGSCGMIGGRPNQALYFI GYVGGEALYLDPHTVQRVGTVGSKQD PAEQELDETFHQRYASRISFTSMDPSLA VCFLCVSRQQFDQLVARFNDSVNGGTS QALFEVTKTRQAPWTPTTASSASSRKN SGPTEAFNVISATEIPNEEFEEVEPRTLD DSDEEFEIIA ENSANGP XP_318212.3 AWGITHISIVDCGHISLSNPIRQSLYRYE 362 00000001364 DTLNGGKPKASTVAERLLEINPSAKITGI [Anopheles NLKIPMPGHPVGQGNEVNETREILTKLI gambiae str. NLIQQHDVIYLLTDSRESRWLPTMLGRF PEST] YNKIVMNAALGFDSYLVMRHGFQTNN IMEADGDTNLSSTVIAGFHKINCCDLGC YFCNDIVAPGNSMKDRTLDQQCTVTRP GVSNMASALAVELMISIIQHGDAPAYY RTPKSDPHAQQQEPEGLLGIIPHSIRGNI STLQSMVTATARYTNCVACSSLVLERY ATSGQDFIINVLNGSESLEAIVGL hypothetical XP_326958.1 MDLKFATFSSEIELPFYSALFSSKLDHD 363 protein KLDSSARPVLGLYEPRSHASPEASTRM [Neurospora QILGSALTSDQDESGPLGMTRAEGYIKN crassa VNTIEEFKNTDKNAMIKKAGEQIWDAI OR74A] QDGTIYSCPSLLASFRILSYADLKKYKF TYWFAFPALHSEPQWKRTGPIGRLTSD ESTALVERIGTWRYMVDRREHGFFLAK KVRREAAGPRSSLDDPGVDIGYRWDIG SLRDFETGFFNDAAEEDRYVAFVDPSN YPEYPSWPLRNLLILIRQRYRLNKVQIL CYRDTQPRRHEARSTILPLAMDQVGDV ELKCMPKVTGWERNGNGDLRPRVANL AEYMDPTRLADQAVDLNLKLMKWRL APNLDLDAIKNTKCLLLGAGTLGSYVS RNLLGWGVRKITFIDYGSVSYSNPVRQ PLFKFEDCHNGGKPKAIQAAEALKEIYP GVDVEGYALSVPMLDHAIHNEAKTKA DFDKLKELIDSHDAIFLLMDTRESRWLP TLMGKAANKIVMNAALGFDTYVVMR HGAAPNDGSEETLGCYFCNDVVVAAD SMKDQTLDQQCTVTRPGVAAIASALLV ELLTSILQHPLKQHAPAPVSTGTGSAVS YERDPPDHPLGLVPHQVRGFLSNFQNM VIRGKSYPQCSACSKPILDAYKEGGWE FVKTALASRDYVAELSGLAEVQRLAEK AAAEMQWSEDEEGMDEEEGEGELI hypothetical XP_330558.1 MFKRHAGPGRGGGGDGALRDNPAMSF 364 protein VLLTESQIASSDALSLQKNNRSSAQDLS [Neurospora SGAYSSNNSNTNNNNVGASEEDDMAN crassa AHLSDQMERILKLFEVISARSDIDHPICI OR74A] ECSDMLVEEMQKKLESANREKDAYVN YLKELKASEPTDEEIRAQEEATRKAKQ AEKELLEELKALEQEQAALEREKLELE AEIREVDIKEEEFWRARNGFNTTLIDFQ NERDSINSKFDHDSRQLEKLQRSNVFN DTFCISHDGTFATINGLRLGRMHNVPV DWPEINAAWGHALLLLVTVAEKLNFRF EGYEPQPMGSTSRIVRIEPASTSMASSF YPSRPVDANAPPPPAKRTVLELYSSGDF PLGFTFIHRKFDTAMVAFLELVRQLGV HVQEQTRREGNPLSLPYQIQGDKISDVS IKLGVQQDDSWAKACKLTLTCCKFLLA HASNSWLHDYDFEAYEILDCILIGENSLG hypothetical XP_331198.1 MADGVIARLMSGGRGARSFYEELRGR 365 protein DNVSDVDDRAGLLDEENLNQHFNDYD [Neurospora LENAEGLRLEDSRATVDGRIPRGRAQL crassa SGRPPRPAATTHWGTSHDDDGDNDVP OR74A] ASLLVERYDRGAAPLGSPGKPRSQHAG SRAHPAPGLSKGRTHQQRPHIDQELQPP LHSDAAPSSLLAGAITGNAKKMAEWR WANITNLDSFMQDVYSYYRGSGMWCI VVERVLHLIKVAFVAFLLTFLSQCVDFK KIPSNQKLSQVLVPQCTRNMSGLWNIG LWLFAFYFMWKSIQYILDLRRLTHVRD FYIHLLNIPDEDMQTITWQEVVARIMVL RDQNVRTTRTITPQNQRWVLGSQSKER LDASDIANRLMRRENYMIAMINKDILD LTIPLPILRNRQLLSQTLEWTLMFSILDF VFDPKGQVHQEFLRSDRRGILSAKLRSR FIFAGVMILILSPFVAGYLIIVYFLEYYN EIQKNPSILSARSYTPLAEWKFREFNELP HLFKRRLDMSHPFASHYIDQFPKAKTS MVAKTVSFIAGSIATVLALISVFDPEMF LGFEITHDRTVLFYTAVFGAIWSVARGS VSEDNAVFDPEYALGNVVEYTHYQPEH WKDRWHSADVKAEFEELYKLKLVIFIE EILSILTTPFVLFFSLPKSADQIIDFFREFT IHVDGLGYVCYFAEFDFKKGSKSQAPA ATAGEGDVRDDYYSTKHGKMEASMY GFINNYARNPKHLPPAMRQQFHLPPVF PGITSPTLAGDLAASRMGRSQRGRSKG PLPSRTPRPGAVMAEPSPMASILLDPRH QPIFPNNMSFVNTGHQFRGGNQGDGH MMGGGSMEEDVKGAARHGQQTHDDE SEDSRAGLDESAWQVSPTKDLSRENSG RGLDSVVGEEAGNGAGVVHMLYQFNQ AHLNRRLGGVR hypothetical XP_361151.2 MFCQKCRTPLKLDGSLDDLNPAAYDLL 366 protein VTTSSQQQAHKDATSLSSPNPAHVHDQ MGG_03694 NRKAAYESAIKNAIGSPTFKRRSDITGL [Magnaporthe RGDKAMRDSSMSFILLEESQIAPSRHGA grisea AGRSSGPASPNASKGSAATPAADDDSA 70-15] NETNRMLRLFEILSARSDIDHPVCVECT DILVEGLRKRLESASRERTTYVNFLKKL ELESPTDDELKAQEEALAKAKEQEAAA LKELVALEKEKASLDDEILALEEESRRM DAEEEQFWRERNAFASQLADFQNERDS INSKYDHDARLLQSLQRTNVYNDTFLIS HDGTFATINGLRLGRLHNTPVDWPEIN AAWGHALLLVATVADKLQYRFDGYEP QPMGSMSRIIRFEPPSPAASRVGSAPPQ APKKKVLELYSSGDMPLGLTFMHRKL DAAMVAYLELVRQLGMFMVRTTTAN GKPLTLPYVIDGDKINGVSIKLGIAQDD AWTKACKFVLTCCKFLLAHASNISTMA NGRGKVLGSSST hypothetical XP_364714.1 MASNIFSRLVPQDRGRSFYEDLRQTDP 367 protein DADLESRAGIDIDEENLNRSYHDYDLD MGG_09559 EAERLAGDESHISHSRGDVAGANTVHR [Magnaporthe RGQKANTARWLGAGVEDDVDNDVPES grisea LLVETPRAPQHLLLSPSRAGPSHPRPTA 70-15] VPGPSTRQNQAQWEATRHQQRLHNDD TMPHGPFSGRAGQGRPEPPPVGLMAGD PYEQAMWRWVNVSNLDNFIKDVYAY YRAAGFWCIIVQRILELVNAAFVAVFLT FLSQCVDYHKLPHSKKMEDIIIPKCTQN MSLVWNVGLWLFAIYFICRCFGLIIQLR QLKHLRDFYTHLLKIPEADMQSVSWQD VVGRIMALRDSHPRTAGNLTRVQRAWI GSQSKERLDAHDIANRIMRRENFMIAM LNKDVLDLTIPLPFFRNKQHMSECVVL AISFSILDFVFDNQGQVNPEFLKASRRR QLSQKLKSRFFFAGLMIFVMSPFIALYLI LVYFLTYFHEFRNDPGALGARTYNSLA KWKFREFNELDHLFNDRMNMSHPFAK RYIDMFPKRKTEQVARTVSFITGSIVAV LGLATIFDSEAFLTFEITPDRSVLFYVSIL ATLWAVARGNISDDNEVYDPEFAMKSI IEFTHYEPDHWRGRLHSTEVKNEFSELY KPRPQIFLEEILSILLTPLVLLVSLPNSTD QIVDFFREFTIHVDGLGYVCLFSVFNFQ QGHANQKQAAAADAPDNREEYYSTKH GKMAASFYGFLDHYVINPKTGLPGNQL PGSRQQFQHPPSFPGLQSPTLAADMRHS RMMRERGRSSGVQIQGSQGRTPQFRTP MPQPSPMASILLDPHHQPAPGAFGSRS MHRSRQMAVPHRGGYMSDRDIIEEAV TEDGQDDARFGKLGDEDIDESGGALDE STWQTSPTKTLSRENSGANPQETEVGV LGLIHQFQQAHMHLRR hypothetical XP_367372.2 MSGNDEAAAAGVAPPQTLQFAPFESQI 368 protein EMPFYSALFSRKLDHDKLDDSVRPVIG MGG_07297 LYQPMSERPPAESTRMQIQGGALSSSH [Magnaporthe VPMGYTRADGSIRNFNTIEDFKKADKG grisea AILRQAGAQIWDAIKDGSIYEIPSLLSSF 70-15] AILSYADLKKYRFTYWFAYPTLHSVPA WRRDGPLARFSSKETTALVNEVGTFRY AHDTRQHGFFLAKKVPYRSGPFRRGLP RDDSDGDDIGFTWSIGALGEFEKGFFK GIKEEDQYIAFVDSSSYAENPSWPLRNL LVLIRQRFQLQKANILCYRDTQARRDEP RSIVLPLASEGPATPQTSEMPKVTGWER HPSSKLQARVISLAEYMDPTRIADQAV DLNLKLMKWRISPKLDLEAMRSLKCLL LGAGTLGSYVSRNLMGWGVRKITFVD YGNVSFSNPVRQPLFEFEDCLSGGVPK APKAAEALKKINPGVEAEGHVLSVPML GHPVLNEAQTKEDFEKLQQLIKAHDVV FLLMDTRESRWLPTVMGKAEGKIVMN AALGFDTYVVMRHGAAPKDGTESTLG CYFCNDVVAPSDSMKDQTLDQQCTVT RPGVAAIASAMLVEMLTSVLQHPQREH APAPKATGPPGNPEYQRDPPDHALGIVP HQVRGFLANFQNMIISGESYPNCSACSS PIVGAYKSDGWEFVKKALSDKDYVLEL SGLAEVQRQAEAMQNEVDWDEDEDV AAAEEGDGEML PREDICTED: XP_417327.2 MPSDRAFKQRRTFADRCKEVQQIREQH 369 hypothetical PNKIPVIIERYKGEKQLPVLDKTKFLVP protein DHVNMSELVKIIRRRLQLNPTQAFFLLV [Gallus NQHSMVSVSTPISEIYEQEKDEDGFLYM gallus] VYASQETFGY PREDICTED: XP_419549.2 MQAGPGVQAVRPFKLRKSLATRREEV 370 similar AGIRAKFPTKIPVIVERYQKEKYLPLLD to MAP1 KTKFLVPEELTMTQFITIIRSRMALTATQ light chain AFYLLVNNKSLASMSLTMAEVYRDYK 3-like DEDGFVYMTYASQEMFGCCSLTLGKT protein 2 MECHHKT [Gallus gallus] PREDICTED: XP_424902.2 MSCSMAVEEDFFLEEKRFKQYCEEFVK 371 hypothetical HSQQIGDGWEWRTTKDLGDGYLSKTH protein FQVTNKSISPDLKKENGSTEQTLLTHVE [Gallus ESSDDSQVAGVCATEEVIRYEYHVLYS gallus] SSYQVPVLYFRACFLDGRPLTLDEIWKS VHVCYQARLQEGPWDTITQQEHPLLGQ PFFVLHPCRTNEFMCSILAGSQKDNRHR NYIVLWLSTVGPVVGLTLPLSYAKLEPE ENTNAEID unnamed XP_455132.1 MTDLTLRCMHCHSMLEIDVSLMDLSM 372 protein AQRDLLVSSDANTSGKDSSANSNQIPA product DKLKVMKEVKQPSQLRLTKPGNIASDS [Kluyveromyces YVFLTDTEYSLQKSKIGGDESGDEEDY lactis] DDRNKTLSSRINALGNIFNILSSKNNVD YPVCQGCCDTLLEKLKEEYNQELKKRD TYHDFMKRIQEHKNVNGINIGDNRALE ELSSLKKEKEQLLRELQRLEDEDEKLQ KETILLQEELAKKKDQYIVRLQKQNIQE LEQLTFIKDVQSLKNQRVVTLNHIDKLR KLNIYNETFRISHDGPFGTINDLKLGSVP NASVPWSEINSALGQVVLLLSLIAEKLS VSFTDYKLIPMGSTSSIEKFDPKTNQWF VHKAFSGDEFSFGSLFHKESAIDKALTC ILEIISLLSAKVSSDSQDPASIELPYEILG DKINGLTILLNGATPSLEWTTSCKFLLT NVKWLLAFSTAHIDKNKP PREDICTED: XP_534391.2 MPSDRPFKQRRTFADRCKEVQQIRDQH 373 similar PSKIPVIIERYKGEKQLPVLDKTKFLVPD to HVNMSELVKIIRRRLQLNPTQAFFLLVN microtubule- QHSMVSVSTPIADIYEQEKDDDGFLYM associated VYASQETFGF protein 1 light chain 3 alpha isoform 1 [Canis familiaris] PREDICTED: XP_584030.2 MQTPQKSPSLRPFKQRKSLATRREEVA 374 similar GIRVKFPGKIPVIVERYPREKFLPRLDKT to MAP1 KFLVPQELTMTQFLSVIRSRMVLGATE light chain AFYLLVNNKSLGSMNVTMAEIYRDYK 3-like DEDGFVYMTYASQEMFGCLGSAAPED protein 2 ASSLGEDRPCHPL isoform 1 [Bos taurus] PREDICTED: XP_699602.3 MSDNAESPTENPKDEHSLQHAVTDHSE 375 ATG12 SSDEKKKIDVLLKAVGDTPIMKTKKWS autophagy VERRRTIQSLAQFISRFLKLEPSEQLFIY related 12 VNQSFAPSPDQEVGVLFECFGSDGKLV homolog (S. cerevisiae) LHYCKSQAWG [Danio rerio]

TABLE 3 Epitopes that include the phosphorylation site in autophagy proteins. PRODUCT NO NAME Sequence (SEQ ID NO) 1 APG3L-pY18 EVAEX (376), VAEXL (377), AEXLT (378), EXLTP (379), XLTPV X = Tyrosine or (380), LEVAEX (381), EVAEXL (382), VAEXLT (383), AEXLTP Phosphotyrosine (384), EXLTPV (385), XLTPVL (386), LEVAEXL (387), EVAEXLT (388), VAEXLTP (389), AEXLTPV (390), EXLTPVL (391), LEVAEXLT (392), EVAEXLTP (393), VAEXLTPV (394), AEXLTPVL (395), LEVAEXLTP (396), EVAEXLTPV (397), VAEXLTPVL (398), LEVAEXLTPV (399), EVAEXLTPVL (400), LEVAEXLTPVL (401) 2 APG3L-pY160 DMEEX (402), MEEXE (403), EEXEE (404), EXEES (405), XEESG X = Tyrosine or (406), ADMEEX (407), DMEEXE (408), MEEXEE (409), EEXEES Phosphotyrosine (410), EXEESG (411), XEESGL (412), ADMEEXE (413), DMEEXEE (414), MEEXEES (415), EEXEESG (416), EXEESGL (417), ADMEEXEE (418), DMEEXEES (419), MEEXEESG (420), EEXEESGL (421), ADMEEXEES (422), DMEEXEESG (423), MEEXEESGL (424), ADMEEXEESG (425), DMEEXEESGL (426), ADMEEXEESGL (427) 3 APG4A-pS6 ESVLX (428), SVLXK (429), VLXKY (430), LXKYE (431), XKYED X = Serine or (432), MESVLX (433), ESVLXK (434), SVLXKY (435), VLXKYE Phosphoserine (436), LXKYED (437), XKYEDQ (438), MESVLXK (439), ESVLXKY (440), SVLXKYE (441), VLXKYED (442), LXKYEDQ (443), MESVLXKY (444), ESVLXKYE (445), SVLXKYED (446), VLXKYEDQ (447), MESVLXKYE (448), ESVLXKYED (449), SVLXKYEDQ (450), MESVLXKYED (451), ESVLXKYEDQ (452), MESVLXKYEDQ (453) 4 APG4A-pS62 RRKFX (454), RKFXP (455), KFXPI (456), FXPIG (457), XPIGG X = Serine or (458), YRRKFX (459), RRKFXP (460), RKFXPI (461), KFXPIG (462), Phosphoserine FXPIGG (463), XPIGGT (464), YRRKFXP (465), RRKFXPI (466), RKFXPIG (467), KFXPIGG (468), FXPIGGT (469), YRRKFXPI (470), RRKFXPIG (471), RKFXPIGG (472), KFXPIGGT (473), YRRKFXPIG (474), RRKFXPIGG (475), RKFXPIGGT (476), YRRKFXPIGG (477), RRKFXPIGGT (478), YRRKFXPIGGT (479) 5 APG4A-pS100 GRDWX (480), RDWXW (481), DWXWE (482), WXWEK (483), X = Serine or XWEKQ (484), LGRDWX (485), GRDWXW (486), RDWXWE (487), Phosphoserine DWXWEK (488), WXWEKQ (489), XWEKQK (490), LGRDWXW (491), GRDWXWE (492), RDWXWEK (493), DWXWEKQ (494), WXWEKQK (495), LGRDWXWE (496), GRDWXWEK (497), RDWXWEKQ (498), DWXWEKQK (499), LGRDWXWEK (500), GRDWXWEKQ (501), RDWXWEKQK (502), LGRDWXWEKQ (503), GRDWXWEKQK (504), LGRDWXWEKQK (505) 6 APG4B-pS121 DRKDX (506), RKDXY (507), KDXYY (508), DXYYS (509), XYYSI X = Serine or (510), IDRKDX (511), DRKDXY (512), RKDXYY (513), KDXYYS Phosphoserine (514), DXYYSI (515), XYYSIH (516), IDRKDXY (517), DRKDXYY (518), RKDXYYS (519), KDXYYSI (520), DXYYSIH (521), IDRKDXYY (522), DRKDXYYS (523), RKDXYYSI (524), KDXYYSIH (525), IDRKDXYYS (526), DRKDXYYSI (527), RKDXYYSIH (528), IDRKDXYYSI (529), DRKDXYYSIH (530), IDRKDXYYSIH (531) 7 APG4B-pS309 PCRMX (532), CRMXI (533), RMXIA (534), MXIAE (535), XIAEL X = Serine or (536), PPCRMX (537), PCRMXI (538), CRMXIA (539), RMXIAE Phosphoserine (540), MXIAEL (541), XIAELD (542), PPCRMXI (543), PCRMXIA (544), CRMXIAE (545), RMXIAEL (546), MXIAELD (547), PPCRMXIA (548), PCRMXIAE (549), CRMXIAEL (550), RMXIAELD (551), PPCRMXIAE (552), PCRMXIAEL (553), CRMXIAELD (554), PPCRMXIAEL (555), PCRMXIAELD (556), PPCRMXIAELD (557) 8 APG4C-pS166 EASLX (558), ASLXG (559), SLXGE (560), LXGER (561), XGERE X = Serine or (562), FEASLX (563), EASLXG (564), ASLXGE (565), SLXGER Phosphoserine (566), LXGERE (567), XGEREF (568), FEASLXG (569), EASLXGE (570), ASLXGER (571), SLXGERE (572), LXGEREF (573), FEASLXGE (574), EASLXGER (575), ASLXGERE (576), SLXGEREF (577), FEASLXGER (578), EASLXGERE (579), ASLXGEREF (580), FEASLXGERE (581), EASLXGEREF (582), FEASLXGEREF (583) 9 APG4C-pS177 TPTIX (584), PTIXL (585), TIXLK (586), IXLKE (587), XLKET (588), X = Serine or KTPTIX (589), TPTIXL (590), PTIXLK (591), TIXLKE (592), Phosphoserine IXLKET (593), XLKETI (594), KTPTIXL (595), TPTIXLK (596), PTIXLKE (597), TIXLKET (598), IXLKETI (599), KTPTIXLK (600), TPTIXLKE (601), PTIXLKET (602), TIXLKETI (603), KTPTIXLKE (604), TPTIXLKET (605), PTIXLKETI (606), KTPTIXLKET (607), TPTIXLKETI (608), KTPTIXLKETI (609) 10 APG4C-pS224 YGKKX (610), GKKXG (611), KKXGK (612), KXGKK (613), X = Serine or XGKKA (614), EYGKKX (615), YGKKXG (616), GKKXGK (617), Phosphoserine KKXGKK (618), KXGKKA (619), XGKKAG (620), EYGKKXG (621), YGKKXGK (622), GKKXGKK (623), KKXGKKA (624), KXGKKAG (625), EYGKKXGK (626), YGKKXGKK (627), GKKXGKKA (628), KKXGKKAG (629), EYGKKXGKK (630), YGKKXGKKA (631), GKKXGKKAG (632), EYGKKXGKKA (633), YGKKXGKKAG (634), EYGKKXGKKAG (635) 11 APG4C-pS398 FKRAX (636), KRAXE (637), RAXEE (638), AXEEI (639), XEEIT X = Serine or (640), DFKRAX (641), FKRAXE (642), KRAXEE (643), RAXEEI Phosphoserine (644), AXEEIT (645), XEEITK (646), DFKRAXE (647), FKRAXEE (648), KRAXEEI (649), RAXEEIT (650), AXEEITK (651), DFKRAXEE (652), FKRAXEEI (653), KRAXEEIT (654), RAXEEITK (655), DFKRAXEEI (656), FKRAXEEIT (657), KRAXEEITK (658), DFKRAXEEIT (659), FKRAXEEITK (660), DFKRAXEEITK (661) 12 APG4C-S408 MLKFX (662), LKFXS (663), KFXSK (664), FXSKE (665), XSKEK X = Serine or (666), KMLKFX (667), MLKFXS (668), LKFXSK (669), KFXSKE Phosphoserine (670), FXSKEK (671), XSKEKY (672), KMLKFXS (673), MLKFXSK (674), LKFXSKE (675), KFXSKEK (676), FXSKEKY (677), KMLKFXSK (678), MLKFXSKE (679), LKFXSKEK (680), KFXSKEKY (681), KMLKFXSKE (682), MLKFXSKEK (683), LKFXSKEKY (684), KMLKFXSKEK (685), MLKFXSKEKY (686), KMLKFXSKEKY (687) 13 APG4C-pS451 LKRFX (688), KRFXT (689), RFXTE (690), FXTEE (691), XTEEF X = Serine or (692), QLKRFX (693), LKRFXT (694), KRFXTE (695), RFXTEE Phosphoserine (696), FXTEEF (697), XTEEFV (698), QLKRFXT (699), LKRFXTE (700), KRFXTEE (701), RFXTEEF (702), FXTEEFV (703), QLKRFXTE (704), LKRFXTEE (705), KRFXTEEF (706), RFXTEEFV (707), QLKRFXTEE (708), LKRFXTEEF (709), KRFXTEEFV (710), QLKRFXTEEF (711), LKRFXTEEFV (712), QLKRFXTEEFV (713) 14 APG4D-S15 YRSSX (714), RSSXP (715), SSXPE (716), SXPED (717), XPEDA X = Serine or (718), QYRSSX (719), YRSSXP (720), RSSXPE (721), SSXPED (722), Phosphoserine SXPEDA (723), XPEDAR (724), QYRSSXP (725), YRSSXPE (726), RSSXPED (727), SSXPEDA (728), SXPEDAR (729), QYRSSXPE (730), YRSSXPED (731), RSSXPEDA (732), SSXPEDAR (733), QYRSSXPED (734), YRSSXPEDA (735), RSSXPEDAR (736), QYRSSXPEDA (737), YRSSXPEDAR (738), QYRSSXPEDAR (739) 15 APG4D-pS341 KPRHX (740), PRHXL (741), RHXLY (742), HXLYF (743), XLYFI X = Serine or (744), GKPRHX (745), KPRHXL (746), PRHXLY (747), RHXLYF Phosphoserine (748), HXLYFI (749), XLYFIG (750), GKPRHXL (751), KPRHXLY (752), PRHXLYF (753), RHXLYFI (754), HXLYFIG (755), GKPRHXLY (756), KPRHXLYF (757), PRHXLYFI (758), RHXLYFIG (759), GKPRHXLYF (760), KPRHXLYFI (761), PRHXLYFIG (762), GKPRHXLYFI (763), KPRHXLYFIG (764), GKPRHXLYFIG (765) 16 APG4D-pS467 AKRPX (766), KRPXS (767), RPXSE (768), PXSED (769), XSEDF X = Serine or (770), RAKRPX (771), AKRPXS (772), KRPXSE (773), RPXSED Phosphoserine (774), PXSEDF (775), XSEDFV (776), RAKRPXS (777), AKRPXSE (778), KRPXSED (779), RPXSEDF (780), PXSEDFV (781), RAKRPXSE (782), AKRPXSED (783), KRPXSEDF (784), RPXSEDFV (785), RAKRPXSED (786), AKRPXSEDF (787), KRPXSEDFV (788), RAKRPXSEDF (789), AKRPXSEDFV (790), RAKRPXSEDFV (791) 17 APG5L-pY35 EAEPX (792), AEPXY (793), EPXYL (794), PXYLL (795), XYLLL X = Tyrosine or (796), REAEPX (797), EAEPXY (798), AEPXYL (799), EPXYLL Phosphotyrosine (800), PXYLLL (801), XYLLLP (802), REAEPXY (803), EAEPXYL (804), AEPXYLL (805), EPXYLLL (806), PXYLLLP (807), REAEPXYL (808), EAEPXYLL (809), AEPXYLLL (810), EPXYLLLP (811), REAEPXYLL (812), EAEPXYLLL (813), AEPXYLLLP (814), REAEPXYLLL (815), EAEPXYLLLP (816), REAEPXYLLLP (817) 18 APG5L-pS225 EVCPX (818), VCPXA (819), CPXAI (820), PXAID (821), XAIDP X = Serine or (822), KEVCPX (823), EVCPXA (824), VCPXAI (825), CPXAID Phosphoserine (826), PXAIDP (827), XAIDPE (828), KEVCPXA (829), EVCPXAI (830), VCPXAID (831), CPXAIDP (832), PXAIDPE (833), KEVCPXAI (834), EVCPXAID (835), VCPXAIDP (836), CPXAIDPE (837), KEVCPXAID (838), EVCPXAIDP (839), VCPXAIDPE (840), KEVCPXAIDP (841), EVCPXAIDPE (842), KEVCPXAIDPE (843) 19 APG7L-pS95 NTLEX (844), TLEXF (845), LEXFK (846), EXFKT (847), XFKTA X = Serine or (848), TNTLEX (849), NTLEXF (850), TLEXFK (851), LEXFKT Phosphoserine (852), EXFKTA (853), XFKTAD (854), TNTLEXF (855), NTLEXFK (856), TLEXFKT (857), LEXFKTA (858), EXFKTAD (859), TNTLEXFK (860), NTLEXFKT (861), TLEXFKTA (862), LEXFKTAD (863), TNTLEXFKT (864), NTLEXFKTA (865), TLEXFKTAD (866), TNTLEXFKTA (867), NTLEXFKTAD (868), TNTLEXFKTAD (869) 20 APG7L-pS173 DQRFX (870), QRFXL (871), RFXLK (872), FXLKQ (873), XLKQI X = Serine or (874), LDQRFX (875), DQRFXL (876), QRFXLK (877), RFXLKQ Phosphoserine (878), FXLKQI (879), XLKQIE (880), LDQRFXL (881), DQRFXLK (882), QRFXLKQ (883), RFXLKQI (884), FXLKQIE (885), LDQRFXLK (886), DQRFXLKQ (887), QRFXLKQI (888), RFXLKQIE (889), LDQRFXLKQ (890), DQRFXLKQI (891), QRFXLKQIE (892), LDQRFXLKQI (893), DQRFXLKQIE (894), LDQRFXLKQIE (895) 22 APG8b-pT12 KQRRX (896), QRRXF (897), RRXFE (898), RXFEQ (899), XFEQR X = Threonine (900), FKQRRX (901), KQRRXF (902), QRRXFE (903), RRXFEQ or (904), RXFEQR (905), XFEQRV (906), TFKQRRX (907), FKQRRXF Phosphothreonine (908), KQRRXFE (909), QRRXFEQ (910), RRXFEQR (911), RXFEQRV (912), TFKQRRXF (913), FKQRRXFE (914), KQRRXFEQ (915), QRRXFEQR (916), RRXFEQRV (917), TFKQRRXFE (918), FKQRRXFEQ (919), KQRRXFEQR (920), QRRXFEQRV (921), TFKQRRXFEQ (922), FKQRRXFEQR (923), KQRRXFEQRV (924), TFKQRRXFEQR (925), FKQRRXFEQRV (926), TFKQRRXFEQRV (927) 23 APG8b-pS101 EVYEX (928), VYEXE (929), YEXEK (930), EXEKD (931), XEKDE X = Serine or (932), SEVYEX (933), EVYEXE (934), VYEXEK (935), YEXEKD Phosphoserine (936), EXEKDE (937), XEKDED (938), SEVYEXE (939), EVYEXEK (940), VYEXEKD (941), YEXEKDE (942), EXEKDED (943), SEVYEXEK (944), EVYEXEKD (945), VYEXEKDE (946), YEXEKDED (947), SEVYEXEKD (948), EVYEXEKDE (949), VYEXEKDED (950), SEVYEXEKDE (951), EVYEXEKDED (952), SEVYEXEKDED (953) 25 APG8c-pS137 PRDGX (954), RDGXS (955), DGXSL (956), GXSLE (957), XSLED X = Serine or (958), PRDGXS (959), RDGXSL (960), DGXSLE (961), GXSLED Phosphoserine (962), XSLEDR (963), PRDGXSL (964), RDGXSLE (965), DGXSLED (966), GXSLEDR (967), XSLEDRP (968), PRDGXSLE (969), RDGXSLED (970), DGXSLEDR (971), GXSLEDRP (972), PRDGXSLED (973), RDGXSLEDR (974), DGXSLEDRP (975), PRDGXSLEDR (976), RDGXSLEDRP (977), PRDGXSLEDRP (978) 26 APG8c- PRDGXX (979), RDGXXL (980), DGXXLE (981), GXXLED (982), pS137/138 XXLEDR (983), PRDGXXL (984), RDGXXLE (985), DGXXLED X = Serine or (986), GXXLEDR (987), XXLEDRP (988), PRDGXXLE (989), Phosphoserine RDGXXLED (990), DGXXLEDR (991), GXXLEDRP (992), XXLEDRP (993), PRDGXXLED (994), RDGXXLEDR (995), DGXXLEDRP (996), GXXLEDRP (997), PRDGXXLEDR (998), RDGXXLEDRP (999), DGXXLEDRP (1000), PRDGXXLEDRP (1001), RDGXXLEDRP (999), PRDGXXLEDRP (1001) 27 APG8c-pS138 RDGSX (1002), DGSXL (1003), GSXLE (1004), SXLED (1005), X = Serine or XLEDR (1006), PRDGSX (1007), RDGSXL (1008), DGSXLE (1009), Phosphoserine GSXLED (1010), SXLEDR (1011), XLEDRP (1012), PRDGSXL (1013), RDGSXLE (1014), DGSXLED (1015), GSXLEDR (1016), SXLEDRP (1017), PRDGSXLE (1018), RDGSXLED (1019), DGSXLEDR (1020), GSXLEDRP (1021), PRDGSXLED (1022), RDGSXLEDR (1023), DGSXLEDRP (1024), PRDGSXLEDR (1025), RDGSXLEDRP (1026), PRDGSXLEDRP (1027) 28 APG9L1-pS14 RLEAX (1028), LEAXY (1029), EAXYS (1030), AXYSD (1031), X = Serine or XYSDS (1032), QRLEAX (1033), RLEAXY (1034), LEAXYS (1035), Phosphoserine EAXYSD (1036), AXYSDS (1037), XYSDSP (1038), QRLEAXY (1039), RLEAXYS (1040), LEAXYSD (1041), EAXYSDS (1042), AXYSDSP (1043), QRLEAXYS (1044), RLEAXYSD (1045), LEAXYSDS (1046), EAXYSDSP (1047), QRLEAXYSD (1048), RLEAXYSDS (1049), LEAXYSDSP (1050), QRLEAXYSDS (1051), RLEAXYSDSP (1052), QRLEAXYSDSP (1053) 29 APG9L1-pY209 ELDIX (1054), LDIXH (1055), DIXHR (1056), IXHRI (1057), XHRIL X = Tyrosine or (1058), TELDIX (1059), ELDIXH (1060), LDIXHR (1061), DIXHRI Phosphotyrosine (1062), IXHRIL (1063), XHRILR (1064), TELDIXH (1065), ELDIXHR (1066), LDIXHRI (1067), DIXHRIL (1068), IXHRILR (1069), TELDIXHR (1070), ELDIXHRI (1071), LDIXHRIL (1072), DIXHRILR (1073), TELDIXHRI (1074), ELDIXHRIL (1075), LDIXHRILR (1076), TELDIXHRIL (1077), ELDIXHRILR (1078), TELDIXHRILR (1079) 30 APG9L1-pS613 QSLQX (1080), SLQXE (1081), LQXES (1082), QXESE (1083), X = Serine or XESEP (1084), IQSLQX (1085), QSLQXE (1086), SLQXES (1087), Phosphoserine LQXESE (1088), QXESEP (1089), XESEPL (1090), IQSLQXE (1091), QSLQXES (1092), SLQXESE (1093), LQXESEP (1094), QXESEPL (1095), IQSLQXES (1096), QSLQXESE (1097), SLQXESEP (1098), LQXESEPL (1099), IQSLQXESE (1100), QSLQXESEP (1101), SLQXESEPL (1102), IQSLQXESEP (1103), QSLQXESEPL (1104), IQSLQXESEPL (1105) 31 APG9L1-pS735 HRREX (1106), RREXD (1107), REXDE (1108), EXDES (1109), X = Serine or XDESG (1110), WHRREX (1111), HRREXD (1112), RREXDE (1113), Phosphoserine REXDES (1114), EXDESG (1115), XDESGE (1116), WHRREXD (1117), HRREXDE (1118), RREXDES (1119), REXDESG (1120), EXDESGE (1121), WHRREXDE (1122), HRREXDES (1123), RREXDESG (1124), REXDESGE (1125), WHRREXDES (1126), HRREXDESG (1127), RREXDESGE (1128), WHRREXDESG (1129), HRREXDESGE (1130), WHRREXDESGE (1131) 32 APG9L1-pS738 ESDEX (1132), SDEXG (1133), DEXGE (1134), EXGES (1135), X = Serine or XGESA (1136), RESDEX (1137), ESDEXG (1138), SDEXGE (1139), Phosphoserine DEXGES (1140), EXGESA (1141), XGESAP (1142), RESDEXG (1143), ESDEXGE (1144), SDEXGES (1145), DEXGESA (1146), EXGESAP (1147), RESDEXGE (1148), ESDEXGES (1149), SDEXGESA (1150), DEXGESAP (1151), RESDEXGES (1152), ESDEXGESA (1153), SDEXGESAP (1154), RESDEXGESA (1155), ESDEXGESAP (1156), RESDEXGESAP (1157) 33 APG9L1-pS741 ESGEX (1158), SGEXA (1159), GEXAP (1160), EXAPD (1161), X = Serine or XAPDE (1162), DESGEX (1163), ESGEXA (1164), SGEXAP (1165), Phosphoserine GEXAPD (1166), EXAPDE (1167), XAPDEG (1168), DESGEXA (1169), ESGEXAP (1170), SGEXAPD (1171), GEXAPDE (1172), EXAPDEG (1173), DESGEXAP (1174), ESGEXAPD (1175), SGEXAPDE (1176), GEXAPDEG (1177), DESGEXAPD (1178), ESGEXAPDE (1179), SGEXAPDEG (1180), DESGEXAPDE (1181), ESGEXAPDEG (1182), DESGEXAPDEG (1183) 34 APG9L1-pS828 PEEGX (1184), EEGXE (1185), EGXED (1186), GXEDE (1187), X = Serine or XEDEL (1188), VPEEGX (1189), PEEGXE (1190), EEGXED (1191), Phosphoserine EGXEDE (1192), GXEDEL (1193), XEDELP (1194), VPEEGXE (1195), PEEGXED (1196), EEGXEDE (1197), EGXEDEL (1198), GXEDELP (1199), VPEEGXED (1200), PEEGXEDE (1201), EEGXEDEL (1202), EGXEDELP (1203), VPEEGXEDE (1204), PEEGXEDEL (1205), EEGXEDELP (1206), VPEEGXEDEL (1207), PEEGXEDELP (1208), VPEEGXEDELP (1209) 35 APG10L-pS116 YFRAX (1210), FRAXF (1211), RAXFL (1212), AXFLD (1213), X = Serine or XFLDG (1214), LYFRAX (1215), YFRAXF (1216), FRAXFL (1217), Phosphoserine RAXFLD (1218), AXFLDG (1219), XFLDGR (1220), LYFRAXF (1221), YFRAXFL (1222), FRAXFLD (1223), RAXFLDG (1224), AXFLDGR (1225), LYFRAXFL (1226), YFRAXFLD (1227), FRAXFLDG (1228), RAXFLDGR (1229), LYFRAXFLD (1230), YFRAXFLDG (1231), FRAXFLDGR (1232), LYFRAXFLDG (1233), YFRAXFLDGR (1234), LYFRAXFLDGR (1235) 36 APG12L-pS26 LTDVX (1236), TDVXP (1237), DVXPE (1238), VXPET (1239), X = Serine or XPETT (1240), GLTDVX (1241), LTDVXP (1242), TDVXPE (1243), Phosphoserine DVXPET (1244), VXPETT (1245), XPETTT (1246), GLTDVXP (1247), LTDVXPE (1248), TDVXPET (1249), DVXPETT (1250), VXPETTT (1251), GLTDVXPE (1252), LTDVXPET (1253), TDVXPETT (1254), DVXPETTT (1255), GLTDVXPET (1256), LTDVXPETT (1257), TDVXPETTT (1258), GLTDVXPETT (1259), LTDVXPETTT (1260), GLTDVXPETTT (1261) 37 APG12L-pS41 SAAVX (1262), AAVXP (1263), AVXPG (1264), VXPGT (1265), X = Serine or XPGTE (1266), SSAAVX (1267), SAAVXP (1268), AAVXPG (1269), Phosphoserine AVXPGT (1270), VXPGTE (1271), XPGTEE (1272), SSAAVXP (1273), SAAVXPG (1274), AAVXPGT (1275), AVXPGTE (1276), VXPGTEE (1277), SSAAVXPG (1278), SAAVXPGT (1279), AAVXPGTE (1280), AVXPGTEE (1281), SSAAVXPGT (1282), SAAVXPGTE (1283), AAVXPGTEE (1284), SSAAVXPGTE (1285), SAAVXPGTEE (1286), SSAAVXPGTEE (1287) 38 APG16L-pS213 NEKDX (1288), EKDXR (1289), KDXRR (1290), DXRRR (1291), X = Serine or XRRRQ (1292), ENEKDX (1293), NEKDXR (1294), EKDXRR (1295), Phosphoserine KDXRRR (1296), DXRRRQ (1297), XRRRQA (1298), CENEKDX (1299), ENEKDXR (1300), NEKDXRR (1301), EKDXRRR (1302), KDXRRRQ (1303), DXRRRQA (1304), CENEKDXR (1305), ENEKDXRR (1306), NEKDXRRR (1307), EKDXRRRQ (1308), KDXRRQA (1309), CENEKDXRR (1310), ENEKDXRRR (1311), NEKDXRRRQ (1312), EKDXRRRQA (1313), CENEKDXRRR (1314), ENEKDXRRRQ (1315), NEKDXRRRQA (1316), CENEKDXRRR (1317), ENEKDXRRRQ (1318), NEKDXRRRQA (1319), CENEKDXRRRQ (1320), ENEKDXRRRQA (1321), CENEKDXRRRQA (1322) 39 APG16L-pS287 FGRRX (1323), GRRXV (1324), RRXVS (1325), RXVSS (1326), X = Serine or XVSSF (1327), IFGRRX (1328), FGRRXV (1329), GRRXVS (1330), Phosphoserine RRXVSS (1331), RXVSSF (1332), XVSSFP (1333), IFGRRXV (1334), FGRRXVS (1335), GRRXVSS (1336), RRXVSSF (1337), RXVSSFP (1338), IFGRRXVS (1339), FGRRXVSS (1340), GRRXVSSF (1341), RRXVSSFP (1342), IFGRRXVSS (1343), FGRRXVSSF (1344), GRRXVSSFP (1345), IFGRRXVSSF (1346), FGRRXVSSFP (1347), IFGRRXVSSFP (1348) 40 APG16L-pS304 THPGX (1349), HPGXG (1350), PGXGK (1351), GXGKE (1352), X = Serine or XGKEV (1353), DTHPGX (1354), THPGXG (1355), HPGXGK (1356), Phosphoserine PGXGKE (1357), GXGKEV (1358), XGKEVR (1359), DTHPGXG (1360), THPGXGK (1361), HPGXGKE (1362), PGXGKEV (1363), GXGKEVR (1364), DTHPGXGK (1365), THPGXGKE (1366), HPGXGKEV (1367), PGXGKEVR (1368), DTHPGXGKE (1369), THPGXGKEV (1370), HPGXGKEVR (1371), DTHPGXGKEV (1372), THPGXGKEVR (1373), DTHPGXGKEVR (1374) 41 BECN1-pS64 EETNX (1375), ETNXG (1376), TNXGE (1377), NXGEE (1378), X = Serine or XGEEP (1379), EEETNX (1380), EETNXG (1381), ETNXGE (1382), Phosphoserine TNXGEE (1383), NXGEEP (1384), XGEEPF (1385), EEETNXG (1386), EETNXGE (1387), ETNXGEE (1388), TNXGEEP (1389), NXGEEPF (1390), EEETNXGE (1391), EETNXGEE (1392), ETNXGEEP (1393), TNXGEEPF (1394), EEETNXGEE (1395), EETNXGEEP (1396), ETNXGEEPF (1397), EEETNXGEEP (1398), EETNXGEEPF (1399), EEETNXGEEPF (1400) 42 BECN1-pT72 PFIEX (1401), FIEXP (1402), IEXPR (1403), EXPRQ (1404), XPRQD X = Threonine (1405), EPFIEX (1406), PFIEXP (1407), FIEXPR (1408), IEXPRQ or (1409), EXPRQD (1410), XPRQDG (1411), EPFIEXP (1412), Phosphothreonine PFIEXPR (1413), FIEXPRQ (1414), IEXPRQD (1415), EXPRQDG (1416), XPRQDGV (1417), EPFIEXPR (1418), PFIEXPRQ (1419), FIEXPRQD (1420), IEXPRQDG (1421), EXPRQDGV (1422), EPFIEXPRQ (1423), PFIEXPRQD (1424), FIEXPRQDG (1425), IEXPRQDGV (1426), EPFIEXPRQD (1427), PFIEXPRQDG (1428), FIEXPRQDGV (1429), EPFIEXPRQDG (1430), PFIEXPRQDGV (1431), EPFIEXPRQDGV (1432) 43 BECN1-pS249 DELKX (1433), ELKXV (1434), LKXVE (1435), KXVEN (1436), X = Serine or XVENQ (1437), DDELKX (1438), DELKXV (1439), ELKXVE (1440), Phosphoserine LKXVEN (1441), KXVENQ (1442), XVENQM (1443), DDELKXV (1444), DELKXVE (1445), ELKXVEN (1446), LKXVENQ (1447), KXVENQM (1448), DDELKXVE (1449), DELKXVEN (1450), ELKXVENQ (1451), LKXVENQM (1452), DDELKXVEN (1453), DELKXVENQ (1454), ELKXVENQM (1455), DDELKXVENQ (1456), DELKXVENQM (1457), DDELKXVENQM (1458)

TABLE 4 Epitopes that include the phosphorylation site in autophagy proteins. PRODUCT NAME/ SEQ NO Phosphorylation Site X equals Sequence ID NO 1 APG3L-Tyrosine 18 Tyrosine or Phosphotyrosine LEVAEXLTPVL 401 2 APG3L-Tyrosine 160 Tyrosine or Phosphotyrosine ADMEEXEESGL 427 3 APG4A-Serine 6 Serine or Phosphoserine MESVLXKYEDQ 453 4 APG4A-Serine 62 Serine or Phosphoserine YRRKFXPIGGT 479 5 APG4A-Serine 100 Serine or Phosphoserine LGRDWXWEKQK 505 6 APG4B-Serine 121 Serine or Phosphoserine IDRKDXYYSIH 531 7 APG4B-Serine 309 Serine or Phosphoserine PPCRMXIAELD 557 8 APG4C-Serine 166 Serine or Phosphoserine FEASLXGEREF 583 9 APG4C-Serine 177 Serine or Phosphoserine KTPTIXLKETI 609 10 APG4C-Serine 224 Serine or Phosphoserine EYGKKXGKKAG 635 11 APG4C-Serine 398 Serine or Phosphoserine DFKRAXEEITK 661 12 APG4C-Serine 408 Serine or Phosphoserine KMLKFXSKEKY 687 13 APG4C-Serine 451 Serine or Phosphoserine QLKRFXTEEFV 713 14 APG4D-Serine 15 Serine or Phosphoserine QYRSSXPEDAR 739 15 APG4D-Serine 341 Serine or Phosphoserine GKPRHXLYFIG 765 16 APG4D-Serine 467 Serine or Phosphoserine RAKRPXSEDFV 791 17 APG5L-Tyrosine 35 Tyrosine or Phosphotyrosine REAEPXYLLLP 817 18 APG5L-Serine 225 Serine or Phosphoserine KEVCPXAIDPE 843 19 APG7L-Serine 95 Serine or Phosphoserine TNTLEXFKTAD 869 20 APG7L-Serine 173 Serine or Phosphoserine LDQRFXLKQIE 895 22 APG8b-Tyrosine 12 Tyrosine or Phosphotyrosine TFKQRRXFEQRV 927 23 APG8b-Serine 101 Serine or Phosphoserine SEVYEXEKDED 953 25 APG8c-Serine 137 Serine or Phosphoserine PRDGXSLEDRP 978 26 APG8c-Serine 137/138 Serine or Phosphoserine PRDGXXLEDRP 1001 27 APG8c-Serine 138 Serine or Phosphoserine PRDGSXLEDRP 1027 28 APG9L1-Serine 14 Serine or Phosphoserine QRLEAXYSDSP 1053 29 APG9L1-Tyrosine 209 Tyrosine or Phosphotyrosine TELDIXHRILR 1079 30 APG9L1-Serine 613 Serine or Phosphoserine IQSLQXESEPL 1105 31 APG9L1-Serine 735 Serine or Phosphoserine WHRREXDESGE 1131 32 APG9L1-Serine 738 Serine or Phosphoserine RESDEXGESAP 1157 33 APG9L1-Serine 741 Serine or Phosphoserine DESGEXAPDEG 1183 34 APG9L1-Serine 828 Serine or Phosphoserine VPEEGXEDELP 1209 35 APG10L-Serine 116 Serine or Phosphoserine LYFRAXFLDGR 1235 36 APG12L-Serine 26 Serine or Phosphoserine GLTDVXPETTT 1261 37 APG12L-Serine 41 Serine or Phosphoserine SSAAVXPGTEE 1287 38 APG16L-Serine 213 Serine or Phosphoserine CENEKDSRRRQA 25 39 APG16L-Serine 287 Serine or Phosphoserine IFGRRXVSSFP 1459 40 APG16L-Serine 304 Serine or Phosphoserine DTHPGXGKEVR 1374 41 BECN1-Serine 64 Serine or Phosphoserine EEETNXGEEPF 1460 42 BECN1-Tyrosine 72 Tyrosine or Phosphotyrosine EPFIEXPRQDGV 1461 43 BECN1-Serine 249 Serine or Phosphoserine DDELKXVENQM 1458

TABLE 5 Amino Acid Sequences Showing Phosphorylation Sites Gene Name/ NO Phosphorylation Site Sequence SEQ ID NO 1 APG3L-pY18 LEVAEYLTPVL 1462 2 APG3L-pY160 ADMEEYEESGL 1463 3 APG4A-pS6 MESVLSKYEDQ 1464 4 APG4A-pS62 YRRKFSPIGGT 1465 5 APG4A-pS100 LGRDWSWEKQK 1466 6 APG4B-pS121 IDRKDSYYSIH 1467 7 APG4B-pS309 PPCRMSIAELD 1468 8 APG4C-pS166 FEASLSGEREF 1469 9 APG4C-pS177 KTPTISLKETI 1470 10 APG4C-pS224 EYGKKSGKKAG 1471 11 APG4C-pS398 DFKRASEEITK 1472 12 APG4C-S408 KMLKFSSKEKY 1473 13 APG4C-pS451 QLKRFSTEEFV 1474 14 APG4D-S15 QYRSSSPEDAR 1475 15 APG4D-pS341 GKPRHSLYFIG 1476 16 APG4D-pS467 RAKRPSSEDFV 1477 17 APG5L-pY35 REAEPYYLLLP 1478 18 APG5L-pS225 KEVCPSAIDPE 1479 19 APG7L-pS95 TNTLESFKTAD 1480 20 APG7L-pS173 LDQRFSLKQIE 1481 22 APG8b-pT12 TFKQRRTFEQRV 1482 23 APG8b-pS101 SEVYESEKDED 1483 25 APG8c-pS137 PRDGSSLEDRP 1484 26 APG8c-pS137/138 PRDGBSLEDRP 1485 27 APG8c-pS138 PRDGSSLEDRP 1486 28 APG9L1-pS14 QRLEASYSDSP 1487 29 APG9L1-pY209 TELDIYHRILR 1488 30 APG9L1-pS613 IQSLQSESEPL 1489 31 APG9L1-pS735 WHRRESDESGE 1490 32 APG9L1-pS738 RESDESGESAP 1491 33 APG9L1-pS741 DESGESAPDEG 1492 34 APG9L1-pS828 VPEEGSEDELP 1493 35 APG10L-pS116 LYFRASFLDGR 1494 36 APG12L-pS26 GLTDVSPETTT 1495 37 APG12L-pS41 SSAAVSPGTEE 1496 38 APG16L-pS213 CENEKDSRRRQA 25 39 APG16L-pS287 IFGRRSVSSFP 1497 40 APG16L-pS304 DTHPGSGKEVR 1498 41 BECN1-pS64 EEETNSGEEPF 1499 42 BECN1-pT72 EPFIETPRQDGV 1500 43 BECN1-pS249 DDELKSVENQM 1501

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1. An isolated autophagy peptide comprising an amino acid sequence selected from the group consisting of sequences set forth in Table 1, wherein the x residue is nonphosphorylated or phosphorylated serine, threonine, or tyrosine, and with the proviso that the peptide is not a full-length autophagy protein.
 2. An isolated autophagy peptide of claim 1 wherein the peptide does not comprise a sequence set forth in Table
 2. 3. The isolated autophagy peptide of claim 1, which comprises an amino acid sequence selected from the group consisting of the sequences set forth in Table
 3. 4. The isolated autophagy peptide of claim 1, which comprises an amino acid sequence selected from the group consisting of sequences set forth in Table
 1. 5. The isolated autophagy peptide of claim 4, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine.
 6. The isolated autophagy peptide of claim 1, wherein the x residue is phosphorylated serine, threonine, or tyrosine.
 7. A method for producing an antibody to an autophagy polypeptide, which method comprises: (a) introducing an isolated autophagy peptide of claim 1 to a mammal in an amount sufficient to produce an antibody to said autophagy peptide; and (b) recovering said antibody from said mammal.
 8. The method of claim 7, wherein the x residue in the isolated autophagy peptide is nonphosphorylated serine, threonine, or tyrosine and the method is used to produce an antibody to a nonphosphorylated autophagy polypeptide.
 9. The method of claim 7, wherein the x residue in the isolated autophagy peptide is phosphorylated serine, threonine, or tyrosine and the method is used to produce an antibody to a phosphorylated autophagy polypeptide.
 10. A method for detecting an autophagy protein or fragment comprising an amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated or nonphosphorylated serine, threonine, or tyrosine in a sample, which method comprises: (a) contacting a sample containing or suspected of containing an autophagy protein or fragment comprising the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated or nonphosphorylated serine, threonine, or tyrosine, with an isolated antibody that specifically binds to an epitope that comprises the amino acid residue x in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated or nonphosphorylated serine, threonine, or tyrosine; and (b) assessing a complex formed between said autophagy protein or fragment, if present in said sample, and said antibody, to determine the presence, absence and/or amount of said autophagy protein or fragment in said sample.
 11. The method of claim 10, wherein the epitope comprises the amino acid residue x in the amino acid sequence set forth in Table 4 and an amino acid residue of the autophagy protein that is outside the amino acid sequence set forth in Table
 4. 12. The method of claim 10, wherein the epitope comprises the amino acid residue x in the amino acid sequence set forth in Table 4 and amino acid residues of the autophagy protein that are outside the amino acid sequence set forth in Table
 4. 13. The method of claim 10, wherein the epitope is comprised in the amino acid sequence set forth in Table
 4. 14. The method of claim 10, wherein the epitope is comprised in an amino acid sequence set forth in Table
 3. 15. The method of claim 10, wherein the epitope is comprised in an amino acid sequence selected from the sequence set forth in Table
 1. 16. The method of claim 10, wherein the isolated antibody specifically binds to the epitope that comprises the x residue in the amino acid sequence set forth in Table 4, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine.
 17. The method of claim 10, wherein the isolated antibody specifically binds to the epitope that comprises the x residue in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated serine, threonine, or tyrosine.
 18. The method of claim 10, wherein the isolated antibody specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is nonphosphorylated serine, threonine, or tyrosine, but does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4 wherein the x residue is phosphorylated serine, threonine, or tyrosine.
 19. The method of claim 10, wherein the isolated antibody specifically binds to an epitope comprised in the amino acid sequence set forth in Table 4, wherein the x residue is phosphorylated serine, threonine, or tyrosine, but does not specifically bind to an epitope comprised in the amino acid sequence set forth in Table 4 wherein the x residue is nonphosphorylated serine, threonine, or tyrosine. 